Редактирование: BDNF

Brain-derived neurotrophic factor precursor (BDNF) (Abrineurin) [Contains: BDNF precursor form (ProBDNF)]

==Publications==

{{medline-entry
|title=Influence of [i][[BDNF]][/i] Genetic Polymorphisms in the Pathophysiology of Aging-related Diseases.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33269104
|abstract=For the first time in history, most of the population has a life expectancy equal or greater than 60 years. By the year 2050, it is expected that the world population in that age range will reach 2000 million, an increase of 900 million with respect to 2015, which poses new challenges for health systems. In this way, it is relevant to analyze the most common diseases associated with the aging process, namely Alzheimer´s disease, Parkinson Disease and Type II Diabetes, some of which may have a common genetic component that can be detected before manifesting, in order to delay their progress. Genetic inheritance and epigenetics are factors that could be linked in the development of these pathologies. Some researchers indicate that the [i][[BDNF]][/i] gene is a common factor of these diseases, and apparently some of its polymorphisms favor the progression of them. In this regard, alterations in the level of [[BDNF]] expression and secretion, due to polymorphisms, could be linked to the development and/or progression of neurodegenerative and metabolic disorders. In this review we will deepen on the different polymorphisms in the [i][[BDNF]][/i] gene and their possible association with age-related pathologies, to open the possibilities of potential therapeutic targets.

|keywords=* Aging
* BDNF gene
* aging-related diseases
* polymorphism
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673859
}}
{{medline-entry
|title=Dietary fish hydrolysate supplementation containing n-3 LC-PUFAs and peptides prevents short-term memory and stress response deficits in aged mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32976934
|abstract=Brain aging is characterized by a decline in cognitive functions, which can lead to the development of neurodegenerative pathologies. Age-related spatial learning and memory deficits are associated with a chronic low-grade inflammation. Anxiety disorders and stress response alterations, occurring for a part of the elderly, have also been linked to an increased neuroinflammation and thus, an accelerated cognitive decline. Nutrition is an innovative strategy to prevent age-related cognitive impairments. Among the nutrients, n-3 long chain polyunsaturated fatty acids (LC-PUFAs) and low molecular weight peptides from proteins, especially those from marine resources, are good candidates for their immunomodulatory, anxiolytic and neuroprotective properties. The aim of this study is to determine the combined effect of n-3 LC-PUFAs and low molecular weight peptides on cognitive functions, and their mechanism of action. We are the first to show that a dietary supplementation with a fish hydrolysate containing n-3 LC-PUFAs and low molecular weight peptides prevented the age-related spatial short-term memory deficits and modulated navigation strategies adopted during spatial learning. In addition, the fish hydrolysate displayed anxiolytic activities with the reduction of anxiety-like behaviour in aged mice, restored the plasmatic corticosterone levels similar to adult animals following an acute stress and modulated the hypothalamic stress response. These effects on behaviour can be explained by the immunomodulatory and neuroprotective properties of the fish hydrolysate that limited microgliosis in vivo, decreased LPS-induced expression of pro-inflammatory cytokines and increased the expression of growth factors such as [[BDNF]] and [[NGF]] in vitro. Thus, n-3 LC-PUFAs and low molecular weight peptides contained in the fish hydrolysate can play an important role in the limitation of neuroinflammation and stress response alterations during aging and represent a potential strategy for the prevention of age-related cognitive decline.

|keywords=* Aging
* Anxiety-like behaviour
* Cognitive decline
* Hydrolysate
* Low molecular weight peptides
* Marine by-products
* Memory
* Navigation strategies
* Neuroinflammation
* Stress response
* n-3 Long chain polyunsaturated fatty acids (n-3 LC-PUFAs)
|full-text-url=https://sci-hub.do/10.1016/j.bbi.2020.09.022
}}
{{medline-entry
|title=Moderators of the Impact of (Poly)Phenols Interventions on Psychomotor Functions and [[BDNF]]: Insights from Subgroup Analysis and Meta-Regression.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32961777
|abstract=Recent anti-aging interventions have shown contradictory impacts of (poly)phenols regarding the prevention of cognitive decline and maintenance of brain function. These discrepancies have been linked to between-study differences in supplementation protocols. This subgroup analysis and meta-regression aimed to (i) examine differential effects of moderator variables related to participant characteristics and supplementation protocols and (ii) identify practical recommendations to design effective (poly)phenol supplementation protocols for future anti-aging interventions. Multiple electronic databases (Web of Science; PubMed) searched for relevant intervention published from inception to July 2019. Using the PICOS criteria, a total of 4303 records were screened. Only high-quality studies ([i]n[/i] = 15) were included in the final analyses. Random-effects meta-analysis was used, and we calculated standard differences in means (SDM), effect size (ES), and 95% confidence intervals (CI) for two sufficiently comparable items (i.e., psychomotor function and brain-derived neurotrophic factor ([[BDNF]])). When significant heterogeneity was computed ([i]I[/i]  > 50%), a subgroup and meta-regression analysis were performed to examine the moderation effects of participant characteristics and supplementation protocols. The reviewed studies support the beneficial effect of (poly)phenols-rich supplementation on psychomotor functions (ES = -0.677, [i]p[/i] = 0.001) and brain plasticity (ES = 1.168, [i]p[/i] = 0.028). Subgroup analysis revealed higher beneficial impacts of (poly)phenols (i) in younger populations compared to older (SDM = -0.89 vs. -0.47 for psychomotor performance, and 2.41 vs. 0.07 for [[BDNF]], respectively), (ii) following an acute compared to chronic supplementation (SDM = -1.02 vs. -0.43 for psychomotor performance), and (iii) using a phenolic compound with medium compared to low bioavailability rates (SDM = -0.76 vs. -0.68 for psychomotor performance and 3.57 vs. 0.07 for DBNF, respectively). Meta-regressions revealed greater improvement in [[BDNF]] levels with lower percentages of female participants (Q = 40.15, df = 6, [i]p[/i] < 0.001) and a skewed scatter plot toward a greater impact using higher (poly)phenols doses. This review suggests that age group, gender, the used phenolic compounds, their human bioavailability rate, and the supplementation dose as the primary moderator variables relating to the beneficial effects of (poly)phenol consumption on cognitive and brain function in humans. Therefore, it seems more advantageous to start anti-aging (poly)phenol interventions in adults earlier in life using medium (≈500 mg) to high doses (≈1000 mg) of phenolic compounds, with at least medium bioavailability rate (≥9%).

|keywords=* aging
* antioxidant
* brain functions
* brain plasticity
* cognition
* psychomotor functions
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551086
}}
{{medline-entry
|title=[[COX5A]] Plays a Vital Role in Memory Impairment Associated With Brain Aging [i]via[/i] the [[BDNF]]/ERK1/2 Signaling Pathway.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32754029
|abstract=Cytochrome c oxidase subunit Va ([[COX5A]]) is involved in maintaining normal mitochondrial function. However, little is known on the role of [[COX5A]] in the development and progress of Alzheimer's disease (Martinez-Losa et al., 2018). In this study, we established and characterized the genomic profiles of genes expressed in the hippocampus of Senescence-Accelerated Mouse-prone 8 (SAMP8) mice, and revealed differential expression of [[COX5A]] among 12-month-aged SAMP8 mice and 2-month-aged SAMP8 mice. Newly established transgenic mice with systemic [[COX5A]] overexpression (51% increase) resulted in the improvement of spatial recognition memory and hippocampal synaptic plasticity, recovery of hippocampal [[CA1]] dendrites, and activation of the [[BDNF]]/ERK1/2 signaling pathway [i]in vivo[/i]. Moreover, mice with both [[COX5A]] overexpression and [[BDNF]] knockdown showed a poor recovery in spatial recognition memory as well as a decrease in spine density and branching of dendrites in [[CA1]], when compared to mice that only overexpressed [[COX5A]]. [i]In vitro[/i] studies supported that [[COX5A]] affected neuronal growth [i]via[/i] [[BDNF]]. In summary, this study was the first to show that [[COX5A]] in the hippocampus plays a vital role in aging-related cognitive deterioration [i]via[/i] [[BDNF]]/ERK1/2 regulation, and suggested that [[COX5A]] may be a potential target for anti-senescence drugs.

|keywords=* BDNF
* COX5A
* ERK1/2
* brain senescence
* memory impairment
* mitochondria
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365906
}}
{{medline-entry
|title=Electric Stimulation of Neurogenesis Improves Behavioral Recovery After Focal Ischemia in Aged Rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32742258
|abstract=The major aim of stroke therapies is to stimulate brain repair and to improve behavioral recuperation after cerebral ischemia. Despite remarkable advances in cell therapy for stroke, stem cell-based tissue replacement has not been achieved yet stimulating the search for alternative strategies for brain self-repair using the neurogenic zones of the brain, the dentate gyrus and the subventricular zone (SVZ). However, during aging, the potential of the hippocampus and the SVZ to generate new neuronal precursors, declines. We hypothesized that electrically stimulation of endogenous neurogenesis in aged rats could increase the odds of brain self-repair and improve behavioral recuperation after focal ischemia. Following stroke in aged animals, the rats were subjected to two sessions of electrical non-convulsive stimulation using ear-clip electrodes, at 7- and 24 days after MCAO. Animal were sacrificed after 48 days. We report that electrical stimulation (ES) stimulation of post-stroke aged rats led to an improved functional recovery of spatial long-term memory (T-maze) but not on the rotating pole or the inclined plane, both tests requiring complex sensorimotor skills. Surprisingly, ES had a detrimental effect on the asymmetric sensorimotor deficit. Histologically, there was a robust increase in the number of doublecortin-positive cells in the dentate gyrus and SVZ of the infarcted hemisphere and the presence of a considerable number of neurons expressing tubulin beta III in the infarcted area. Among the gene that were unique to ES, we noted increases in the expression of [i]seizure related 6 homolog like[/i] which is one of the physiological substrate of the β-secretase [[BACE1]] involved in the pathophysiology of the Alzheimer's disease and [i]Igfbp3[/i] and [[BDNF]] receptor mRNAs which has been shown to have a neuroprotective effect after cerebral ischemia. However, ES was associated with a long-term down regulation of cortical gene expression after stroke in aged rats suggesting that gene expression in the peri-infarcted cortical area may not be related to electrical stimulation induced-neurogenesis in the subventricular zone and hippocampus.

|keywords=* aging
* behavior
* electrical stimulation
* neurogenesis
* rats
* stroke
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365235
}}
{{medline-entry
|title=Astroglia-Derived [[BDNF]] and MSK-1 Mediate Experience- and Diet-Dependent Synaptic Plasticity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32708382
|abstract=Experience- and diet-dependent regulation of synaptic plasticity can underlie beneficial effects of active lifestyle on the aging brain. Our previous results demonstrate a key role for brain-derived neurotrophic factor ([[BDNF]]) and MSK1 kinase in experience-related homeostatic synaptic scaling. Astroglia has been recently shown to release [[BDNF]] via a calcium-dependent mechanism. To elucidate a role for astroglia-derived [[BDNF]] in homeostatic synaptic plasticity in the aging brain, we explored the experience- and diet-related alterations of synaptic transmission and plasticity in transgenic mice with impairment of the [[BDNF]]/MSK1 pathway (MSK1 kinase dead knock-in mice, MSK1 KD) and impairment of glial exocytosis (dnSNARE mice). We found that prolonged tonic activation of astrocytes caused [[BDNF]]-dependent increase in the efficacy of excitatory synapses accompanied by enlargement of synaptic boutons. We also observed that exposure to environmental enrichment (EE) and caloric restriction (CR) enhanced the Ca  signalling in cortical astrocytes and strongly up-regulated the excitatory and down-regulated inhibitory synaptic currents in old wild-type mice, thus counterbalancing the impact of ageing on astroglial and synaptic signalling. The EE- and CR-induced up-scaling of excitatory synaptic transmission in neocortex was accompanied by the enhancement of long-term synaptic potentiation. Importantly, effects of EE and CR on synaptic transmission and plasticity was significantly reduced in the MSK1 KD and dnSNARE mice. Combined, our results suggest that astroglial release of [[BDNF]] is important for the homeostatic regulation of cortical synapses and beneficial effects of EE and CR on synaptic transmission and plasticity in aging brain.

|keywords=* AMPA receptors
* Arc/Arg3.1
* GABA receptors
* TrkB receptors
* aging
* calcium signalling
* dendritic spines
* diet
* enriched environment
* glia-neuron interactions
* ion conductance microscopy
* synaptic scaling
* synaptic strength
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407492
}}
{{medline-entry
|title=[[BDNF]] reverses aging-related microglial activation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32664974
|abstract=Excessive microglial activation is implicated in the pathogenesis of various age-related neurodegenerative diseases. In addition to neurons, brain-derived neurotrophic factor ([[BDNF]]) and its receptor TrkB are also expressed in microglia. However, the direct effect of [[BDNF]] on age-related microglial activation has rarely been investigated. We began to address this question by examining the effect of age on microglial activation and the [[BDNF]]-TrkB pathway in mice. By using pharmacological and genetic approaches, the roles of [[BDNF]] and downstream signaling pathways in microglial activation and related neurotoxicity were examined in microglial cell line and primary microglial cells. We showed that microglial activation was evident in the brains of aged mice. The levels of [[BDNF]] and TrkB in microglia decreased with age and negatively correlated with their activation statuses in mice during aging. Interestingly, aging-related microglial activation could be reversed by chronic, subcutaneous perfusion of [[BDNF]]. Peripheral lipopolysaccharide (LPS) injection-induced microglial activation could be reduced by local supplement of [[BDNF]], while shTrkB induced local microglial activation in naïve mice. In cultured microglial cell line and primary microglial cells, [[BDNF]] inhibited LPS-induced microglial activation, including morphological changes, activations of p38, JNK, and NF-кB, and productions of proinflammatory cytokines. These effects were blocked by shTrkB. [[BDNF]] induced activations of ErK and CREB which then competed with LPS-induced activation of NF-кB for binding to a common coactivator, CREB-binding protein. Decreasing [[BDNF]]-TrkB signaling during aging favors microglial activation, while upregulation [[BDNF]] signaling inhibits microglial activation via the TrkB-Erk-CREB pathway.

|keywords=* Aging
* BDNF
* CREB
* Microglial activation
* NF-кB
* TrkB
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362451
}}
{{medline-entry
|title=Etanercept improves aging-induced cognitive deficits by reducing inflammation and vascular dysfunction in rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32569601
|abstract=Normal aging may lead to cognitive deficits, which is associated with endothelial dysfunction and neuroinflammation. Dysregulation of [[TNF]]α expression contributes to vascular aging and dementia. In this study, we investigated the effects of etanercept, which is a [[TNF]]α inhibitor, on cognitive and endothelial function in aged rats. Male Wistar albino rats were divided into 3 groups: Young (4 month), aged (24 month) aged ETA (24 month etanercept). Etanercept (0.8 mg/kg/weekly) was given to the aged ETA group subcutaneously for 8 weeks. Then passive avoidance test (PAT) and the Morris water maze test (MWMT) were used to evaluate cognitive functions of rats. After the behavioral tests, the rats were subjected to systolic blood pressure (SBP) measurement, and then endothelial function of thoracic aorta was evaluated by isolated organ bath system. Thoracic eNOS expression, hippocampal [[BDNF]] expression and serum and hippocampal [[TNF]] levels were also measured. In aged rats, it was shown that cognitive performances in MWMT and PAT were abolished whereas SBP unchanged. Furthermore, aging resulted in endothelial dysfunction, decreased expressions of thoracic eNOS and hippocampal [[BDNF]], and increased level of [[TNF]] in serum and hippocampus. In contrast, ETA improved age-related cognitive deficits and endothelial dysfunction. In addition, ETA reversed changes in protein expression in aged rats. The results of this study indicate that ETA prevents cognitive deficits, endothelial dysfunction, peripheral and neuro-inflammation and decreament of neurotrophin expression in aged rats. These findings suggest that ETA may be beneficial with neuroprotective and vasculoprotective effects in elderly patients.

|keywords=* Aging
* Etanercept
* Inflammation
* Learning
* Memory
* TNFα
* Vascular dementia
|full-text-url=https://sci-hub.do/10.1016/j.physbeh.2020.113019
}}
{{medline-entry
|title=High Supervised Resistance Training in Elderly Women: The Role of Supervision Ratio.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32509119
|abstract=The objective of this study was to compare the effects of very high supervision (VHS-RT) versus high supervision (HS-RT) ratio resistance training (RT) on irisin, brain-derived neurotrophic factor (BNDF), muscle strength, functional capacity, and body composition in elderly women. Participants performed daily undulating periodized RT over 16 weeks with two different supervision ratios: VHS-RT at 1:2 (supervisor/subject) or HS-RT at 1:5. Serum was used to analyze brain derived neurotropic factor ([[BDNF]]) and irisin by enzyme-linked immunosorbent assay (ELISA). Body composition was evaluated by dual-energy X-ray absorptiometry, while functional capacity was evaluated using the Six-minute walk test, and Timed Up and Go (TUG). One- repetition maximum (1RM) was determined for bench press and 45° leg press exercises. For both groups, no differences between baseline and post-training were identified for irisin and lean mass ([i]p[/i] > 0.05). Both groups improved bench press 1-RM, 45° leg press 1-RM, and TUG ([i]p[/i] < 0.05). The VHS-RT group displayed higher effect sizes for 1-RM tests. Moreover, only VHS-RT group reduced body fat and body fat percentage ([i]p[/i] < 0.05). In contrast, the HS-RT increased [[BDNF]] ([i]p[/i] < 0.01). In this sense, RT enhances muscle strength and functional capacity in elderly women independent of supervision ratio. A greater supervision ratio during RT may induce more improvements in muscle strength, and body composition than lower supervision ratio during RT.

|keywords=* Aging
* exercise
* functional capacity
* muscle strength
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241618
}}
{{medline-entry
|title=Metformin regulates astrocyte reactivity in Parkinson's disease and normal aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32497590
|abstract=Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to motor symptoms. Despite the remarkable improvements in the management of PD in recent decades, many patients remain significantly disabled. Metformin is a primary medication for the management of type 2 diabetes. We previously showed that co-treatment with metformin and 3,4-dihydroxyphenyl-l-alanine (l-DOPA) prevented the development of l-DOPA-induced dyskinesia in a 6-hydroxydopamine (6-OHDA)-lesioned animal model of PD. However, effects of metformin on PD- and aging-induced genes in reactive astrocytes remain unknown. In this study, we assessed the effect of metformin on motor function, neuroprotection, and reactive astrocytes in the 6-OHDA-induced PD animal model. In addition, the effects of metformin on the genes expressed by specific types of astrocytes were analyzed in PD model and aged mice. Here, we showed that metformin treatment effectively improves the motor symptoms in the 6-OHDA-induced PD mouse model, whereas metformin had no effect on tyrosine hydroxylase-positive neurons. The activation of AMPK and [[BDNF]] signaling pathways was induced by metformin treatment on the 6-OHDA-lesioned side of the striatum. Metformin treatment caused astrocytes to alter reactive genes in a PD animal model. Moreover, aging-induced genes in reactive astrocytes were effectively regulated or suppressed by metformin treatment. Taken together, these results suggest that metformin should be evaluated for the treatment of Parkinson's disease and related neurologic disorders characterized by astrocyte activation.

|keywords=* Aging
* Dorsal striatum
* Metformin
* Parkinson's disease
* Reactive astrocyte
|full-text-url=https://sci-hub.do/10.1016/j.neuropharm.2020.108173
}}
{{medline-entry
|title=Aging-Induced Brain-Derived Neurotrophic Factor in Adipocyte Progenitors Contributes to Adipose Tissue Dysfunction.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32489703
|abstract=Aging-related adipose tissue dysfunction contributes to the progression of chronic metabolic diseases. We investigated the role of age-dependent expression of a neurotrophin, brain-derived neurotrophic factor ([[BDNF]]) in adipose tissue. Pro-[[BDNF]] expression was elevated in epididymal white adipose tissue (eWAT) with advanced age, which was associated with the reduction in sympathetic innervation. Interestingly, [[BDNF]] expression was enriched in PDGFRα  adipocyte progenitors isolated from eWAT, with age-dependent increase in expression. In vitro pro-[[BDNF]] treatment caused apoptosis in adipocytes differentiated from C3H10T1/2 cells, and siRNA knockdown of sortilin mitigated these effects. Tamoxifen-inducible PDGFRα  cell-specific deletion of [[BDNF]] ([[BDNF]]  KO) reduced pro-[[BDNF]] expression in eWAT, prevented age-associated declines in sympathetic innervation and mitochondrial content in eWAT, and improved insulin sensitivity. Moreover, [[BDNF]]  KO mice showed reduced expression of aging-induced inflammation and senescence markers in eWAT. Collectively, these results identified the upregulation of pro-[[BDNF]] expression in adipocyte progenitors as a feature of visceral white adipose tissue aging and suggested that inhibition of [[BDNF]] expression in adipocyte progenitors is potentially beneficial to prevent aging-related adipose tissue dysfunction.

|keywords=* BDNF
* adipocyte progenitors
* adipose tissue
* aging
* sympathetic innervation
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220283
}}
{{medline-entry
|title=The Role of [[BDNF]] on Aging-Modulation Markers.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32397504
|abstract=An important link between brain aging and a class of growth/survival factors called neurotrophins has recently been demonstrated. In particular, brain-derived neurotrophic factor ([[BDNF]]) plays a fundamental role during age-related synaptic loss, preventing cerebral atrophy and cognitive decline. The aim of the present study was to investigate whether the use of low dose [[BDNF]] sequentially kinetic activated (SKA) was able to counteract some mechanisms underlying the degeneration and aging of nervous tissue by increasing endogenous protection mechanisms. Both in vitro and in vivo experiments were performed to assess the ability of [[BDNF]] SKA to protect and regenerate survival-related molecular pathways, studying intestinal absorption in vitro and brain function in vivo. Our pioneering results show that [[BDNF]] SKA is able to induce the endogenous production of [[BDNF]], using its receptor TrkB and influencing the apolipoprotein E expression. Moreover, [[BDNF]] SKA exerted effects on β-Amyloid and Sirtuin 1 proteins, confirming the hypothesis of a fine endogenous regulatory effect exerted by [[BDNF]] SKA in maintaining the health of both neurons and astrocytes. For this reason, a change in [[BDNF]] turnover is considered as a positive factor against brain aging.

|keywords=* BBB
* astrocytes
* brain aging
* in vivo model
* low dose BDNF
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287884
}}
{{medline-entry
|title=Spermidine and spermine delay brain aging by inducing autophagy in SAMP8 mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32268299
|abstract=The natural polyamine spermidine and spermine have been reported to ameliorate aging and aging-induced dementia. However, the mechanism is still confused. An aging model, the senescence accelerated mouse-8 (SAMP8), was used in this study. Novel object recognition and the open field test results showed that oral administration of spermidine, spermine and rapamycin increased discrimination index, modified number, inner squares distance and times. Spermidine and spermine increased the activity of SOD, and decreased the level of MDA in the aging brain. Spermidine and spermine phosphorylate AMPK and regulate autophagy proteins (LC3, Beclin 1 and p62). Spermidine and spermine balanced mitochondrial and maintain energy for neuron, with the regulation of [[MFN1]], [[MFN2]], DRP1, COX IV and ATP. In addition, western blot results (Bcl-2, Bax and Caspase-3, [[NLRP3]], IL-18, IL-1β) showed that spermidine and spermine prevented apoptosis and inflammation, and elevate the expression of neurotrophic factors, including [[NGF]], PSD95and PSD93 and [[BDNF]] in neurons of SAMP8 mice. These results indicated that the effect of spermidine and spermine on anti-aging is related with improving autophagy and mitochondrial function.

|keywords=* aging
* autophagy
* mitochondrial dysfunction
* polyamine
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185103
}}
{{medline-entry
|title=Microglia senescence occurs in both substantia nigra and ventral tegmental area.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32275335
|abstract=During aging humans lose midbrain dopamine neurons, but not all dopamine regions exhibit vulnerability to neurodegeneration. Microglia maintain tissue homeostasis and neuronal support, but microglia become senescent and likely lose some of their functional abilities. Since aging is the greatest risk factor for Parkinson's disease, we hypothesized that aging-related changes in microglia and neurons occur in the vulnerable substantia nigra pars compacta (SNc) but not the ventral tegmental area (VTA). We conducted stereological analyses to enumerate microglia and dopaminergic neurons in the SNc and VTA of 1-, 6-, 9-, 18-, and 24-month-old C57BL/J6 mice using sections double-stained with tyrosine hydroxylase ([[TH]]) and Iba1. Both brain regions show an increase in microglia with aging, whereas numbers of [[TH]]  cells show no significant change after 9 months of age in SNc and 6 months in VTA. Morphometric analyses reveal reduced microglial complexity and projection area while cell body size increases with aging. Contact sites between microglia and dopaminergic neurons in both regions increase with aging, suggesting increased microglial support/surveillance of dopamine neurons. To assess neurotrophin expression in dopaminergic neurons, [[BDNF]] and [[TH]] mRNA were quantified. Results show that the ratio of [[BDNF]] to [[TH]] decreases in the SNc, but not the VTA. Gait analysis indicates subtle, aging-dependent changes in gait indices. In conclusion, increases in microglial cell number, ratio of microglia to dopamine neurons, and contact sites suggest that innate biological mechanisms compensate for the aging-dependent decline in microglia morphological complexity (senescence) to ensure continued neuronal support in the SNc and VTA.

|keywords=* Parkinson's disease
* aging-dependent neurodegeneration
* dopamine neurons
* microglia complexity
* stereological analyses
* tyrosine hydroxylase; microglia senescence
|full-text-url=https://sci-hub.do/10.1002/glia.23834
}}
{{medline-entry
|title=Towards an understanding of the physical activity-[[BDNF]]-cognition triumvirate: A review of associations and dosage.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32171785
|abstract=Physical activity has received substantial research attention due to its beneficial impact on cognition in ageing, particularly via the action of brain-derived neurotrophic factor ([[BDNF]]). It is well established that physical activity can elevate circulating levels of [[BDNF]], and that [[BDNF]] has neurotrophic, neuroprotective and cognitively beneficial properties. Yet, practical implementation of this knowledge is limited by a lack of clarity on context and dose-effect. Against a shifting backdrop of gradually diminishing physical and cognitive capacity in normal ageing, the type, intensity, and duration of physical activity required to elicit elevations in [[BDNF]], and more importantly, the magnitude of [[BDNF]] elevation required for detectable neuroprotection remains poorly characterised. The purpose of this review is to provide an overview of the association between physical activity, [[BDNF]], and cognition, with a focus on clarifying the magnitude of these effects in the context of normative ageing. We discuss the implications of the available evidence for the design of physical activity interventions intended to promote healthy cognitive ageing.
|mesh-terms=* Aging
* Brain-Derived Neurotrophic Factor
* Cognition
* Exercise
* Healthy Aging
* Humans
|keywords=* Ageing
* BDNF
* Brain
* Physical activity
|full-text-url=https://sci-hub.do/10.1016/j.arr.2020.101044
}}
{{medline-entry
|title=Disruption of synaptic expression pattern and age-related DNA oxidation in a neuronal model of lead-induced toxicity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32058320
|abstract=Lead (Pb) is recognized as a potent inducer of synaptic toxicity generally associated with reduced synaptic transmission and increased neuronal fiber excitability, becoming an environmental risk for neurodegenerative processes. Despite numerous toxicological studies on Pb have been directed to the developing brain, attention concerning long-term consequences of pubertal chronic Pb exposure on neuronal activity is still lacking. Thus, we exposed 4-week-old male mice to 0.2 % lead acetate solution for one month, then, conducted behavioral tests or extracted brain homogenate from mice prefrontal cortex (PFC) and hippocampus at the age of 4, 13 and 16-month-old respectively. Our results showed that treated mice exhibited an evident increase in latency to reach platform following pubertal Pb exposure and aging. The increase of 8-OHdG revealed evident neural DNA oxidative damage across time upon pubertal Pb exposure. In the hippocampus of lead exposed mice at three age nodes, the expression of brain-derived neurotrophic factor precursor (pro[[BDNF]]) increased, while that of mature [[BDNF]] (m[[BDNF]]), cAMP-response element binding protein (CREB) and phosphorylated CREB (pCREB) decreased compared with the control group. Furthermore, the expression of [[BACE1]] protein and tau phosphorylation level in PFC and hippocampus increased, [[APP]] mRNAs in PFC and prolonged induction of [[BACE1]] in hippocampus. Our results show that chronic Pb exposure from pubertal stage onward can either initiate divergent synaptic-related gene expression patterns in adulthood or trigger time-course of neurodegenerative profile within the PFC or hippocampus, which can contribute consistent deficits of cognition across subsequent age-nodes.

|keywords=* Aging mice
* Brain-derived neurotrophic factor precursor
* Latent expression pattern
* Lead
* Pubertal exposure
* Synaptic deficits
* Tau phosphorylation
|full-text-url=https://sci-hub.do/10.1016/j.etap.2020.103350
}}
{{medline-entry
|title=Understanding hormone and hormone therapies' impact on the auditory system.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32026519
|abstract=Hormones such as estrogen, progesterone, and aldosterone all demonstrate vital roles in sustaining auditory function through either the maintenance of cochlear neurons, up/down regulation of critical molecules (i.e., IGF-1, [[BDNF]], etc.), or generation of the endocochlear potential. With disease and/or age, hormone expression begins to decline drastically, which ultimately affects cochlear structures and the integrity of cochlear cells. The following review explores the latest findings as well as realistic outcomes for hormone therapy treatment in the auditory system. This information could serve as a potential guide for patients considering hormone therapy as a medicinal choice to alleviate the signs of onset of presbycusis-age-related hearing loss. Additional scientific investigations could also be carried out to further enhance recent findings.

|keywords=* age-related hearing loss
* aging cochlea
* aldosterone
* estrogen
* presbycusis
* progesterone
|full-text-url=https://sci-hub.do/10.1002/jnr.24588
}}
{{medline-entry
|title=Effect of 9 - PAHSA on cognitive dysfunction in diabetic mice and its possible mechanism.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32014256
|abstract=Diabetes mellitus (DM) is currently a major global health problem, which is associated with the development of cognitive dysfunction. However, although numerous clinical drugs for hyperglycemia have been used at present, safer and more effective therapeutic intervention strategies for diabetic cognitive impairments are still a huge challenge. Recently, several studies have indicated that a novel class of branched palmitic acid esters of hydroxyl stearic acids (PAHSAs) may have anti-diabetes and anti-inflammatory effects in insulin-resistant mice. Herein, whether the 9-PAHSA that one of the PAHSAs can attenuates DM-associated cognitive impairment in a mouse model of type 2 diabetes has been investigated. Our results showed that 9-PAHSA mildly prevented deficits of spatial working memory in Y-maze test while reversed the preference bias toward novel mice in Social choice test. Furthermore, the effect of [[REST]] on cognitive impairment of diabetes was explored for the first time. It was found that the expression of [[REST]] in diabetic mice increased, and the expression of target protein [[BDNF]] (Brain-derived neurotrophic factor) was decreased. After administration of 9-PAHSA, the situation was reversed. In summary, we conclude that exogenous supplement of 9-PAHSA can improve DM-related cognitive impairment to some extent, and the protective effect may be associated with decreased [[REST]]/NRSF (repressor element-1 silencing transcription factor/neuron-restrictive silence factor) and upregulated [[BDNF]] expression in frontal cortex.
|mesh-terms=* Aging
* Animals
* Behavior, Animal
* Blood Glucose
* Body Weight
* Brain
* Brain-Derived Neurotrophic Factor
* Cognitive Dysfunction
* Diabetes Mellitus, Experimental
* Exploratory Behavior
* Male
* Memory Disorders
* Mice
* Palmitic Acid
* Repressor Proteins
* Social Behavior
* Spatial Memory
* Stearic Acids
|keywords=* 9-PAHSA
* BDNF
* Diabetes mellitus
* REST
|full-text-url=https://sci-hub.do/10.1016/j.bbrc.2020.01.071
}}
{{medline-entry
|title=Impact of [[BDNF]] and sex on maintaining intact memory function in early midlife.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31948671
|abstract=Sex steroid hormones and neurotrophic factors, such as brain-derived neurotrophic factor ([[BDNF]]), play a significant neuroprotective role in memory circuitry aging. Here, we present findings characterizing the neuroprotective effects of [[BDNF]] on memory performance, as a function of sex and reproductive status in women. Participants (N = 191; mean age = 50.03 ± 2.10) underwent clinical and cognitive testing, fMRI scanning, and hormonal assessments of menopausal staging. Memory performance was assessed with the 6-Trial Selective Reminding Test and the Face-Name Associative Memory Exam. Participants also performed a working memory (WM) N-back task during fMRI scanning. Results revealed significant interactions between menopausal status and [[BDNF]] levels. Only in postmenopausal women, lower plasma [[BDNF]] levels were associated with significantly worse memory performance and altered function in the WM circuitry. [[BDNF]] had no significant impact on memory performance or WM function in pre/perimenopausal women or men. These results suggest that in postmenopausal women, [[BDNF]] is associated with memory performance and memory circuitry function, thus providing evidence of potential sex-dependent factors of risk and resilience for early intervention.
|mesh-terms=* Brain
* Brain-Derived Neurotrophic Factor
* Cognition
* Female
* Humans
* Magnetic Resonance Imaging
* Male
* Memory
* Memory, Short-Term
* Menopause
* Middle Aged
* Neuroprotective Agents
* Neuropsychological Tests
* Reproduction
* Sex Characteristics
|keywords=* Aging
* BDNF
* Hormones
* Memory
* Menopause
* Sex differences
|full-text-url=https://sci-hub.do/10.1016/j.neurobiolaging.2019.12.014
}}
{{medline-entry
|title=Dysregulation of [[BDNF]]/TrkB signaling mediated by NMDAR/Ca /calpain might contribute to postoperative cognitive dysfunction in aging mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31948437
|abstract=Postoperative cognitive decline (POCD) is a recognized clinical phenomenon characterized by cognitive impairments in patients following anesthesia and surgery, yet its underlying mechanism remains unclear. Brain-derived neurotrophic factor ([[BDNF]]) plays an important role in neuronal plasticity, learning, and memory via activation of TrkB-full length (TrkB-FL) receptors. It has been reported that an abnormal truncation of TrkB mediated by calpain results in dysregulation of [[BDNF]]/TrkB signaling and is associated with cognitive impairments in several neurodegenerative disorders. Calpains are Ca -dependent proteases, and overactivation of calpain is linked to neuronal death. Since one source of intracellular Ca  is N-methyl-d-aspartate receptors (NMDARs) related and the function of NMDARs can be regulated by neuroinflammation, we therefore hypothesized that dysregulation of [[BDNF]]/TrkB signaling mediated by NMDAR/Ca /calpain might be involved in the pathogenesis of POCD. In the present study, 16-month-old C57BL/6 mice were subjected to exploratory laparotomy with isoflurane anesthesia to establish the POCD animal model. For the interventional study, mice were treated with either NMDAR antagonist memantine or calpain inhibitor MDL-28170. Behavioral tests were performed by open field, Y maze, and fear conditioning tests from 5 to 8 days post-surgery. The levels of Iba-1, [[GFAP]], interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), NMDARs, calpain, [[BDNF]], TrkB, bax, bcl-2, caspase-3, and dendritic spine density were determined in the hippocampus. Anesthesia and surgery-induced neuroinflammation overactivated NMDARs and then triggered overactivation of calpain, which subsequently led to the truncation of TrkB-FL, [[BDNF]]/TrkB signaling dysregulation, dendritic spine loss, and cell apoptosis, contributing to cognitive impairments in aging mice. These abnormities were prevented by memantine or MDL-28170 treatment. Collectively, our study supports the notion that NMDAR/Ca2 /calpain is mechanistically involved in anesthesia and surgery-induced [[BDNF]]/TrkB signaling disruption and cognitive impairments in aging mice, which provides one possible therapeutic target for POCD.
|mesh-terms=* Aging
* Animals
* Brain-Derived Neurotrophic Factor
* Calcium
* Calpain
* Male
* Membrane Glycoproteins
* Mice
* Mice, Inbred C57BL
* Postoperative Cognitive Complications
* Protein-Tyrosine Kinases
* Receptors, N-Methyl-D-Aspartate
* Signal Transduction
|keywords=* BDNF
* Calpain
* Cognitive dysfunction
* NMDAR
* Neuroinflammatioin
* Surgery
* TrkB
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966800
}}
{{medline-entry
|title=Testosterone replacement causes dose-dependent improvements in spatial memory among aged male rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31901624
|abstract=Testosterone has been shown to have dose-dependent effects on spatial memory in males, but the effects of aging upon this relationship remain unclear. Additionally, the mechanism by which testosterone regulates memory is unknown, but may involve changes in brain-derived neurotrophic factor ([[BDNF]]) within specific brain regions. We tested the effects of age and testosterone on spatial memory among male rats using two spatial memory tasks: an object-location memory task (OLMT) and the radial-arm maze (RAM). Castration had minimal effect on performance on the RAM, but young rats (2 months) performed significantly fewer working memory errors than aged rats (20 months), and aged rats performed significantly fewer reference memory errors. Both age and castration impaired performance on the OLMT, with only the young rats with intact gonads successfully performing the task. Subsequent experiments involved daily injections of either drug vehicle or one of four doses of testosterone propionate (0.125, 0.250, 0.500, and 1.00 mg/rat) given to castrated aged males. On the RAM, a low physiological dose (0.125 mg) and high doses (0.500-1.000 mg) of testosterone improved working memory, while an intermediate dose (0.250 mg) did not. On the OLMT, only the 0.250 mg T group showed a significant increase in exploration ratios from the exposure trials to the testing trials, indicating that this group remembered the position of the objects. Brain tissue (prefrontal cortex, hippocampus, and striatum) was collected from all subjects to assay [[BDNF]]. We found no evidence that testosterone influenced [[BDNF]], indicating that it is unlikely that testosterone regulates spatial memory through changes in [[BDNF]] levels.

|keywords=* Aging
* BDNF
* Object location memory
* Radial arm maze
* Spatial memory
* Testosterone
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080566
}}
{{medline-entry
|title=The effects of aerobic exercise intensity on memory in older adults.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31665610
|abstract=Aerobic exercise may enhance memory in older adults. However, the optimal intensity and underlying mechanism are unclear. This community-based study examined the effect of aerobic exercise intensity on memory and general cognitive abilities. Brain-derived neurotrophic factor ([[BDNF]]) was examined as a potential mechanism. Sixty-four sedentary older adults participated in 1 of 3 groups: ([i]i[/i]) high-intensity interval training (HIIT); ([i]ii[/i]) moderate continuous training (MCT); or ([i]iii[/i]) stretching control (CON). Prior to and following the intervention, high-interference memory was assessed using a Mnemonic Similarity task and executive functions were assessed using Go Nogo and Flanker tasks. HIIT led to the greatest memory performance compared with MCT and CON ([i]F[/i]  = 6.04, [i]p[/i] = 0.004) and greater improvements in memory correlated with greater increases in fitness ([i]r [/i] (46) = 0.27, [i]p[/i] = 0.03). Exercise intensity seemed to matter less for executive functioning, as positive trends were observed for both HIIT and MCT. No significant differences in [[BDNF]] were found between groups. Overall, these results suggest that aerobic exercise may enhance memory in older adults, with the potential for higher intensity exercise to yield the greatest benefit. While our findings suggest that [[BDNF]] does not regulate these adaptations, the mechanisms remain to be determined.   High-intensity interval training results in the greatest memory performance in inactive older adults compared with moderate continuous training or stretching. Improvement in fitness correlates with improvement in memory performance.

|keywords=* BDNF
* activité physique
* aging
* cognition
* entraînement par intervalles de haute intensité
* executive functions
* exercice
* exercise
* fonctions exécutives
* high-intensity interval training
* memory
* mémoire
* physical activity
* vieillissement
|full-text-url=https://sci-hub.do/10.1139/apnm-2019-0495
}}
{{medline-entry
|title=The Psilocybin-Telomere Hypothesis: An empirically falsifiable prediction concerning the beneficial neuropsychopharmacological effects of psilocybin on genetic aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31634774
|abstract=We introduce a novel hypothesis which states that the therapeutic utilisation of psilocybin has beneficial effects on genetic aging. Ex hypothesi, we predict a priori that controlled psilocybin interventions exert quantifiable positive impact on leucocyte telomere length (telomeres are a robust predictor of mortality and multifarious aging-related diseases). Our hypothesising follows the Popperian logic of scientific discovery, viz., bold (and refutable) conjectures form the very foundation of scientific progress. The 'psilocybin-telomere hypothesis' is formalised as a logically valid deductive (syllogistic) argument and we provide substantial evidence to support the underlying premises. Impetus for our theorising derives from a plurality of converging empirical sources indicating that psilocybin has persistent beneficial effects on various aspects of mental health (e.g., in the context of depression, anxiety, PTSD, OCD, addiction, etc.). Additional support is based on a large corpus of studies that establish reliable correlations between mental health and telomere attrition (improved mental health is generally correlated with longer telomeres). Another pertinent component of our argument is based on recent studies which demonstrate that "meditative states of consciousness" provide beneficial effects on genetic aging. Similarly, psilocybin can induce states of consciousness that are neurophysiologically and phenomenologically significantly congruent with meditative states. Furthermore, prior research has demonstrated that a single dose of psilocybin can occasion life-changing transformative experiences (≈ 70% of healthy volunteers rate their experience with psilocybin amongst the five personally most meaningful lifetime events, viz., ranked next to giving birth to a child or losing a loved one). We postulate that these profound psychological events leave quantifiable marks at the molecular genetic/epigenetic level. Given the ubiquitous availability and cost effectiveness of telomere length assays, we suggest that quantitative telomere analysis should be regularly included in future psilocybin studies as an adjunctive biological marker (i.e., to facilitate scientific consilience via methodological triangulation). In order to substantiate the 'psilocybin-telomere hypothesis' potential neuropsychopharmacological, endocrinological, and genetic mechanisms of action are discussed (e.g., HPA-axis reactivity, hippocampal neurogenesis, neurotropic growth factors such as [[BDNF]], 5-HT  receptor agonism, neuroplasticity/synaptoplasticity, brain-wide alterations in neuronal functional connectivity density, involvement of the [[SLC6A4]] serotonin transporter gene, inter alia). The proposed research agenda is thus intrinsically highly interdisciplinary, and it has deep ramifications from a philosophy of science perspective as it connects the epistemic level (qualitative experiential phenomenology) with the ontic level (quantitative molecular genetics) of analysis. In the long term, multidisciplinary and innovative investigations of the 'psilocybin-telomere hypothesis' could contribute to the improvement of senotherapeutic psychological interventions and the identification of novel geroprotective and neuroprotective/restorative pharmaceutical targets to decelerate genetic aging and improve well-being and quality of life during the aging process.
|mesh-terms=* Aging
* Aging, Premature
* Animals
* Anxiety
* Brain-Derived Neurotrophic Factor
* Consciousness
* DNA Methylation
* Depression
* Disease Models, Animal
* Endocrine System
* Humans
* Models, Genetic
* Models, Psychological
* Neurotransmitter Agents
* Oxidative Stress
* Personality
* Psilocybin
* Psychotropic Drugs
* Research Design
* Serotonin Plasma Membrane Transport Proteins
* Stress, Psychological
* Telomere Shortening
|keywords=* Cellular senescence
* Depression
* Epigenetic clock
* Genetic aging
* Life extension
* Neurophenomenology
* Psilocybin
* Rejuvenation
* Rumination
* Senotherapy
* Telomeres
|full-text-url=https://sci-hub.do/10.1016/j.mehy.2019.109406
}}
{{medline-entry
|title=Retrograde axonal transport of [[BDNF]] and pro[[NGF]] diminishes with age in basal forebrain cholinergic neurons.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31574357
|abstract=Basal forebrain cholinergic neurons (BFCNs) are critical for learning and memory and degenerate early in Alzheimer's disease (AD). BFCNs depend for their survival and function on nerve growth factor ([[NGF]]) and brain-derived neurotrophic factor ([[BDNF]]), which are retrogradely transported from BFCN targets. Age is the greatest risk factor for developing AD, yet the influence of age on BFCN axonal transport is poorly understood. To model aging, embryonic rat basal forebrain or cortical neurons were cultured in microfluidic chambers. Senescence-associated beta-galactosidase staining indicated an aging phenotype only in BFCNs cultured for 18  days in vitro. [[BDNF]] axonal transport impairments were observed exclusivley in aged BFCNs. BFCNs displayed robust pro[[NGF]] transport, which also diminished with in vitro age. The expression of [[NGF]] receptor tropomyosin-related kinase-A and [[BDNF]] receptor tropomyosin-related kinase-B also decreased significantly with in vitro age in BFCNs only. These results suggest a unique vulnerability of BFCNs to age-induced transport deficits. These deficits, coupled with the reliance of BFCNs on neurotrophin transport, may explain their vulnerability to age-related neurodegenerative disorders like AD.
|mesh-terms=* Aging
* Alzheimer Disease
* Axonal Transport
* Brain-Derived Neurotrophic Factor
* Cholinergic Neurons
* Humans
* Nerve Growth Factor
* Prosencephalon
|keywords=* Alzheimer's disease
* Axonal transport
* Basal forebrain
* Neurodegeneration
* Neurotrophins
* Trk receptors
|full-text-url=https://sci-hub.do/10.1016/j.neurobiolaging.2019.07.018
}}
{{medline-entry
|title=Protective effects of vitamin D on neurophysiologic alterations in brain aging: role of brain-derived neurotrophic factor ([[BDNF]]).
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31524100
|abstract= Vitamin D has been hypothesized to be main regulator of the aging rate, alongside evidences support its role in neuroprotection. However, data about the protective role of vitamin D against neurophysiologic alterations associated with brain aging is limited. This study investigated the possible protective effects that vitamin D has on brain-derived neurotrophic factor ([[BDNF]]), cholinergic function, oxidative stress and apoptosis in aging rat brain.   Male Wister albino rats aged 5 months (young), 12 months (middle aged) and 24 months (old) ([i]n[/i] = 20 each) were used. Each age group subdivided to either vitamin D3 supplementation (500 IU/kg/day orally for 5 weeks) or no supplementation (control) group ([i]n[/i] = 10 each). Serum 25-hydroxyvitamin D [25(OH)D], brain [[BDNF]] and malondialdehyde levels and activities of acetylcholinesterase (AChE), antioxidant enzymes (glutathione reductase, glutathione peroxidase and superoxide dismutase) and caspase-3 were quantified.   Vitamin D supplementation significantly mitigated the observed aging-related reduction in brain [[BDNF]] level and activities of AChE and antioxidant enzymes and elevation in malondialdehyde level and caspase-3 activity compared to control groups. Brain [[BDNF]] level correlated positively with serum 25(OH) D level and brain AChE activity and negatively with brain malondialdehyde level and caspase-3 activity in supplemented groups.   Restoring vitamin D levels may, therefore, represent a useful strategy for healthy brain aging. Augmenting brain [[BDNF]] seems to be a key mechanism through which vitamin D counteracts age-related brain dysfunction.

|keywords=* BDNF
* Brain aging
* neurophysiologic alterations
* neuroprotection
* vitamin D supplementation
|full-text-url=https://sci-hub.do/10.1080/1028415X.2019.1665854
}}
{{medline-entry
|title=Differential Effects of Physical Exercise, Cognitive Training, and Mindfulness Practice on Serum [[BDNF]] Levels in Healthy Older Adults: A Randomized Controlled Intervention Study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31498125
|abstract=Previous studies have indicated that an active lifestyle is associated with better brain health and a longer life, compared to a more sedentary lifestyle. These studies, both on human and animal subjects, have typically focused on a single activity, usually physical exercise, but other activities have received an increasing interest. One proposed mechanism is that physical exercise increases levels of brain-derived neurotrophic factor ([[BDNF]]) in the brain. For the first time, the long-term effects on serum [[BDNF]] levels were compared in persons who engaged in either physical exercise training, cognitive training, or mindfulness practice during 5 weeks, and compared with an active control group. Two cohorts of healthy older individuals, one from the Boston area in the US and one from the Växjö area in Sweden, participated. A total of 146 participants were randomly assigned to one of the four groups. All interventions were structurally similar, using interactive, computer-based software that directed participants to carry out specified activities for 35 minutes/day, 5 days per week for 5 weeks. Blood samples were obtained at baseline and soon after the completion of the 5-week long intervention program, and serum [[BDNF]] levels were measured using a commercially available ELISA. Only the group that underwent cognitive training increased their serum [[BDNF]] levels after 5 weeks of training (F1,74 = 4.22, p = 0.044, partial η2 = 0.054), corresponding to an average 10% increase. These results strongly suggest that cognitive training can exert beneficial effects on brain health in an older adult population.
|mesh-terms=* Aged
* Brain-Derived Neurotrophic Factor
* Cognition
* Correlation of Data
* Exercise
* Female
* Healthy Aging
* Healthy Lifestyle
* Humans
* Learning
* Male
* Mindfulness
* Neuropsychological Tests
* Outcome Assessment, Health Care
|keywords=* Aging
* brain-derived neurotrophic factor
* cognitive training
* mindfulness
* physical exercise
|full-text-url=https://sci-hub.do/10.3233/JAD-190756
}}
{{medline-entry
|title=Suppression of gut dysbiosis by Bifidobacterium longum alleviates cognitive decline in 5XFAD transgenic and aged mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31413350
|abstract=To understand the role of commensal gut bacteria on the progression of cognitive decline in Alzheimer's disease via the microbiota-gut-brain axis, we isolated anti-inflammatory Bifidobacterium longum (NK46) from human gut microbiota, which potently inhibited gut microbiota endotoxin production and suppressed NF-κB activation in lipopolysaccharide (LPS)-stimulated BV-2 cells, and examined whether NK46 could simultaneously alleviate gut dysbiosis and cognitive decline in male 5xFAD-transgenic (5XFAD-Tg, 6 months-old) and aged (18 months-old) mice. Oral administration of NK46 (1 × 10  CFU/mouse/day for 1 and 2 months in aged and Tg mice, respectively) shifted gut microbiota composition, particularly Proteobacteria, reduced fecal and blood LPS levels, suppressed NF-κB activation and [[TNF]]-α expression, and increased tight junction protein expression in the colon of 5XFAD-Tg and aged mice. NK46 treatment also alleviated cognitive decline in 5XFAD-Tg and aged mice. Furthermore, NK46 treatment suppressed amyloid-β, β/γ-secretases, and caspase-3 expression and amyloid-β accumulation in the hippocampus of 5XFAD-Tg mice. NK46 treatment also reduced Iba1 , LPS /CD11b , and caspase-3 /NeuN  cell populations and suppressed NF-κB activation in the hippocampus of 5XFAD-Tg and aged mice, while [[BDNF]] expression was increased. These findings suggest that the suppression of gut dysbiosis and LPS production by NK46 can mitigate cognitive decline through the regulation of microbiota LPS-mediated NF-κB activation.
|mesh-terms=* Aging
* Animals
* Bifidobacterium longum
* Cognitive Dysfunction
* Dysbiosis
* Feces
* Gastrointestinal Microbiome
* Humans
* Lipopolysaccharides
* Mice
* Mice, Transgenic
* Probiotics

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694197
}}
{{medline-entry
|title=Dietary Supplementation with Fish Oil or Conjugated Linoleic Acid Relieves Depression Markers in Mice by Modulation of the Nrf2 Pathway.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31398773
|abstract=Inflammation and oxidative stress play an important role in the pathogenesis of depressive disorders and nuclear erythroid related factor 2 (Nrf2), a regulator of RedOx homeostasis and inflammation, is a promising target for depression prevention/treatment. As fish oil (FO) and conjugated linoleic acid (CLA) are known Nrf2 inducers, their protective ability is comparatively evaluated in a murine model of depression (MRL/MpJ-Fas  ). Oxidative stress, fatty acids content, and critical factors reflecting brain functioning-namely brain-derived neurotrophic factor ([[BDNF]]), synaptic markers, and cholinergic signaling-are preliminarily evaluated in the frontal cortex of 8-week (Young) and in 22-week old animals (Old), which are used as model of depression. These markers are measured in Old mice at the end of a 5-week pretreatment with FO or CLA (728 or 650 mg kg  , respectively). Old mice exhibit disrupted Redox homeostasis, compensatory Nrf2 hyperactivation, lower docosaheaxaenoic acid (DHA), and lower [[BDNF]] and synaptic function proteins compared to Young mice. FO and CLA treatment relieves almost all the pathophysiological hallmarks at a level comparable to Young mice. Presented data provide the first evidence for the comparable efficacy of FO or CLA supplementation in preventing depression signs in Old MRL/lpr mice, likely through their ability of improving Nrf2-mediated antioxidant defenses.
|mesh-terms=* Aging
* Animals
* Antidepressive Agents
* Autoimmunity
* Biomarkers
* Brain
* Brain-Derived Neurotrophic Factor
* Depression
* Dietary Supplements
* Docosahexaenoic Acids
* Fatty Acid Elongases
* Fatty Acids
* Fish Oils
* Inflammation
* Linoleic Acids, Conjugated
* Liver
* Male
* Mice, Inbred MRL lpr
* NF-E2-Related Factor 2
* Oxidative Stress
* Stearoyl-CoA Desaturase
* Tumor Necrosis Factor-alpha
|keywords=* brain derived neurotrophic factor
* brain fatty acid profile
* conjugated linoleic acid
* depression
* fish oil
* nuclear erythroid related factor-2
|full-text-url=https://sci-hub.do/10.1002/mnfr.201900243
}}
{{medline-entry
|title=Neuroprotective Biomarkers and Cognitive Function in a Long-Term Prospective Population-based Study of Aging US Adults.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31385821
|abstract=Relationships between brain-derived neurotrophic factor ([[BDNF]]), insulin-like growth factor (IGF-1), aldosterone, and cognition in aging were evaluated in the population-based Epidemiology of Hearing Loss Study (1993 to present). Beginning in 1998 to 2000, cognitive impairment was assessed by report of physician diagnoses and the Mini-Mental State Examination. In 2009 to 2010 and 2013 to 2016, information was collected on diagnosis of mild cognitive impairment/dementia. Decline in cognitive function was assessed by principal component analysis from additional tests administered during 2009 to 2010 and 2013 to 2016. [[BDNF]], IGF-1, and aldosterone were measured in serum collected in 1998 to 2000. There were 1970 participants (mean age=66.9 y; 59.1% female) without cognitive impairment at baseline. Among women, low [[BDNF]] was associated with 16-year incident cognitive impairment [hazard ratio=1.76; 95% confidence interval (CI)=1.04, 2.98]. Among men, increasing IGF-1 was associated with decreased risk [per SD: relative risk (RR)=0.57; 95% CI=0.35, 0.92], whereas increasing aldosterone levels were associated with increased risk (per SD: RR=1.28; 95% CI=1.01, 1.62) for 5-year incident mild cognitive impairment/dementia. Overall, low [[BDNF]] was associated with increased risk (RR=1.52; 95% CI=1.02, 2.26) for 5-year cognitive decline. Low levels of serum [[BDNF]] and IGF-1 were associated with poorer cognition during aging. There may be differential biomarker effects by sex.
|mesh-terms=* Aged
* Aging
* Aldosterone
* Biomarkers
* Brain-Derived Neurotrophic Factor
* Cognition
* Cognitive Dysfunction
* Female
* Humans
* Insulin-Like Growth Factor I
* Longitudinal Studies
* Male
* Neuropsychological Tests
* Prospective Studies
* Protective Factors
* United States

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995426
}}
{{medline-entry
|title=URB597 ameliorates the deleterious effects induced by binge alcohol consumption in adolescent rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31374324
|abstract=Heavy episodic drinking or binge drinking during adolescence may elicit serious neurotoxic consequences in cerebral areas (e.g., the prefrontal cortex, i.e., PFC) and the hippocampus, delay the maturation of the brain and increase the probability of drug abuse and dependence. The endocannabinoid system plays an important role in neuroprotection by reducing oxidative stress and neuroinflammation. In the present study, we aimed to investigate whether URB597, an inhibitor of the metabolic enzyme of the endocannabinoid anandamide (AEA), altered the effects of acute and chronic alcohol administration beginning during rat adolescence on recognition memory, neuroinflammation and brain-derived neurotrophic factor ([[BDNF]]) levels. The animals received intraperitoneal injections of URB597 (0.3 mg/Kg) or vehicle followed by the oral administration of ethanol (3 or 6 g/Kg) or distilled water for 3 consecutive days in one week (acute binging) or over 4 weeks (chronic binging). The groups were submitted to the novel object recognition task, and their PFCs and hippocampi were removed for analyses of the cytokine and [[BDNF]] levels. URB597 potentiated long-term memory after the 3 mg/Kg acute alcohol administration. The chronic binge alcohol administration increased the interferon (IFN)-γ and tumor necrosis factor (TNF)-α levels in the PFC and hippocampus and the interleukin (IL)-10 and [[BDNF]] levels in the PFC, and these effects were prevented by URB597. Our results indicate that the neuromodulation facilitated by AEA can reduce the neuroimmune response induced by the chronic administration of alcohol beginning in adolescence in rats.
|mesh-terms=* Aging
* Amidohydrolases
* Animals
* Benzamides
* Binge Drinking
* Brain
* Brain-Derived Neurotrophic Factor
* Carbamates
* Cytokines
* Male
* Rats
* Rats, Wistar
|keywords=* Adolescence
* Alcohol binging
* Endocannabinoid system
* Neuroinflammation
* URB597
|full-text-url=https://sci-hub.do/10.1016/j.neulet.2019.134408
}}
{{medline-entry
|title=Pro-neurocognitive and anti-sarcopenic benefits of one-year metformin therapy in ovariectomized aged mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31357227
|abstract=Health promotion and healthy nutrition significantly increased life expectancy around the world. Aging is associated with an increase in age-related diseases. The use of metformin (Met) as an anti-aging drug has recently been proposed based on its widespread use in clinical practice. Reports have shown that Met acts as an anti-aging agent. In this study, the effects of long-term, 1 year, Met administration on aging-related behaviors and longevity in ovariectomized mice was studied. Met (1 and 10 mg/kg, daily) was administered orally in ovariectomized mice. The anxiety-like behavior, working memory, and physical strength were measured through elevated plus maze, Y-maze, vertical grid holding, and the obligatory swimming capacity tests. Brains were harvested to measure brain-derived neurotrophic factor ([[BDNF]]) level. Also, the Kaplan-Meier survival curves were used to show differences and similarities in survival patterns. Met (10 mg/kg) decreased anxiety-like behaviors as well as increased muscle strength and working memory in the ovariectomized mice. Moreover, Met increased the physical strength and longevity as well as the level of [[BDNF]] in the ovariectomized mice. Our results indicate that Met administration can be an effective strategy for having a healthy aging in the absence of female gonadal hormones and reverses deleterious effects of ovariectomy-induced aging possibly through [[BDNF]].
|mesh-terms=* Aging
* Animals
* Anxiety
* Behavior, Animal
* Brain
* Cognition
* Disease Models, Animal
* Drug Administration Schedule
* Female
* Maze Learning
* Memory, Short-Term
* Metformin
* Mice
* Ovariectomy
* Sarcopenia
* Time Factors
|keywords=* aging
* brain-derived neurotrophic factor
* metformin
* ovariectomy
|full-text-url=https://sci-hub.do/10.1111/1440-1681.13149
}}
{{medline-entry
|title=Ellagic acid dose and time-dependently abrogates d-galactose-induced animal model of aging: Investigating the role of PPAR-γ.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31238053
|abstract=The world's population is becoming aged and the proportion of older persons is growing in almost every country in the world. Ellagic acid (EA) shows abundant pharmacological properties. Therefore, we aimed to determine the mechanism of anti-aging effects of low and high doses of EA. Aging model was induced by d-galactose (DG), and the anti-aging effect of EA alone or in the presence of PPAR-γ antagonist GW9662, and in combination with metformin were evaluated. The activities of ALT, AST, and AChE, the levels of FBS, HbA1c, testosterone and DHEA-SO , MDA, GSH, [[TNF]]-α, IL-6, advanced glycation end products (AGEs), and [[BDNF]] were measured in serum, liver or brain. DG led to increasing in the levels of IL-6, [[TNF]]-α, MDA, AChE, AGEs, ALT, AST, FBS, and HbA1c, in which decrease in the levels of body weight, GSH, [[BDNF]], DHEA-SO4 and testosterone. Metformin (300 mg/kg) abrogated the effects of DG-induced aging model. We also found that the low dose of EA (30 mg/kg) decreases the deteriorative effects of DG-induced aging at 10 weeks of treatment only, however, high dose of EA (100 mg/kg) was effective at both 6 and 10 weeks of treatment. The addition of GW9662 completely reversed the effects of the low dose of EA, but not for the high dose, on DG-induced aging model. We revealed that daily and oral administration of EA provides anti-aging effects at low dose in a PPAR-γ receptor-dependent fashion, but not at the high dose.
|mesh-terms=* Aging
* Anilides
* Animals
* Apoptosis
* Brain
* Ellagic Acid
* Galactose
* Glutathione Peroxidase
* Liver
* Male
* Malondialdehyde
* Metformin
* Mice
* Models, Animal
* Oxidative Stress
* PPAR gamma
* Superoxide Dismutase
* Tumor Necrosis Factor-alpha
|keywords=* Aging
* Anti-inflammatory
* Ellagic acid
* Metformin
* PPAR-γ
* d-Galactose
|full-text-url=https://sci-hub.do/10.1016/j.lfs.2019.116595
}}
{{medline-entry
|title=Astrocyte Function Is Affected by Aging and Not Alzheimer's Disease: A Preliminary Investigation in Hippocampi of 3xTg-AD Mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31244658
|abstract=Old age is a risk factor for Alzheimer's disease (AD), which is characterized by hippocampal impairment together with substantial changes in glial cell functions. Are these alterations due to the disease progression or are they a consequence of aging? To start addressing this issue, we studied the expression of specific astrocytic and microglial structural and functional proteins in a validated transgenic model of AD (3×Tg-AD). These mice develop both amyloid plaques and neurofibrillary tangles, and initial signs of the AD-like pathology have been documented as early as three months of age. We compared male 3×Tg-AD mice at 6 and 12 months of age with their wild-type age-matched counterparts. We also investigated neurons by examining the expression of both the microtubule-associated protein 2 (MAP2), a neuronal structural protein, and the brain-derived neurotrophic factor ([[BDNF]]). The latter is indeed a crucial indicator for synaptic plasticity and neurogenesis/neurodegeneration. Our results show that astrocytes are more susceptible to aging than microglia, regardless of mouse genotype. Moreover, we discovered significant age-dependent alterations in the expression of proteins responsible for astrocyte-astrocyte and astrocyte-neuron communication, as well as a significant age-dependent decline in [[BDNF]] expression. Our data promote further research on the unexplored role of astroglia in both physiological and pathological aging.

|keywords=* 3×Tg-AD mouse
* AQP4
* Alzheimer’s disease
* S100B
* aging
* astrocyte
* brain-derived neurotrophic factor
* connexin-43
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562169
}}
{{medline-entry
|title=Exenatide Reverts the High-Fat-Diet-Induced Impairment of [[BDNF]] Signaling and Inflammatory Response in an Animal Model of Alzheimer's Disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31256135
|abstract=Alzheimer's disease (AD) is a multifactorial condition in which, along with amyloid-β (Aβ) and tau-related pathology, the synergistic activity of co-morbidity factors promote the onset and progression of the disease. Epidemiological evidence indicates that glucose intolerance, deficits in insulin secretion, or type-2 diabetes mellitus (T2DM) participate in increasing cognitive impairment or dementia risk. Insulin plays a pivotal role in the process as the hormone critically regulates brain functioning. GLP-1, the glucagon-like peptide 1, facilitates insulin signaling, regulates glucose homeostasis, and modulates synaptic plasticity. Exenatide is a synthetic GLP-1 analog employed in T2DM. However, exenatide has also been shown to affect the signaling of the brain-derived neurotrophic factor ([[BDNF]]), synaptic plasticity, and cognitive performances in animal models. In this study, we tested whether exenatide exerts neuroprotection in a preclinical AD model set to mimic the clinical complexity of the human disease. We investigated the effects of exenatide treatment in 3xTg-AD mice challenged with a high-fat diet (HFD). Endpoints of the study were variations in systemic metabolism, insulin and neurotrophic signaling, neuroinflammation, Aβ and tau pathology, and cognitive performances. Results of the study indicate that exenatide reverts the adverse changes of [[BDNF]] signaling and the neuroinflammation status of 3xTg-AD mice undergoing HFD without affecting systemic metabolism or promoting changes in cognitive performances.
|mesh-terms=* Alzheimer Disease
* Animals
* Brain
* Brain-Derived Neurotrophic Factor
* Cognitive Dysfunction
* Disease Models, Animal
* Exenatide
* Female
* Glucagon-Like Peptide 1
* Glucose Tolerance Test
* Hypoglycemic Agents
* Insulin
* Insulin Resistance
* Male
* Mice
* Neuroimmunomodulation
* Neuronal Plasticity
* Neuroprotective Agents
* Signal Transduction
|keywords=* Aging
* BDNF
* T2DM
* dementia
* diabetes
* exendin-4
* insulin
* insulin resistance
* neurotrophic factors
|full-text-url=https://sci-hub.do/10.3233/JAD-190237
}}
{{medline-entry
|title=The Impact of Physical Exercise on Brain-Derived Neurotrophic Factor ([[BDNF]]) Level in Elderly Population.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31210810
|abstract=Memory function disorder is a major health problem in geriatric patients. Physical exercise has the potency to decrease the incidence of many degenerative and chronic health problem, related to cognitive deterioration (dementia). This research aimed to observe the effect of physical exercise in various doses and duration on memory function by analysing the role of Brain-Derived Neurotrophic Factor ([[BDNF]]) as a regulatory protein affected by exercise. This was an analytical observational study with a cohort design. Thirty participants were included in each group, classified as exercise and non-exercise group. The exercise was in the form of jogging for at least fifteen minutes every day. The observation was done for sixty days. Cognitive function assessment was done by using the Mini-Mental State Examination (MMSE) questionnaire. Meanwhile, the [[BDNF]] level was assessed by ELISA. Statistical analysis was done using Independent T-test. Exercise group showed better MMSE score (28.56 ± 1.76), and a higher concentration of [[BDNF]] (235.34 ± 12.56 pg/mL), both were statistically significant. Physical exercise was able to maintain geriatric cognitive function performance by [[BDNF]] protein regulation.

|keywords=* Brain-Derived Neurotrophic Factor
* Elderly
* Geriatrics
* Physical exercise
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560287
}}
{{medline-entry
|title=Cardioprotective effects of microRNA-18a on acute myocardial infarction by promoting cardiomyocyte autophagy and suppressing cellular senescence via brain derived neurotrophic factor.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31168354
|abstract=The prevention of cardiovascular diseases is a matter of great concern, of which acute myocardial infarction (AMI) remains one of the leading causes of death resulting in high morbidity worldwide. Emerging evidence highlights the importance of microRNAs (miRNAs) as functional regulators in cardiovascular disease. In this study, an AMI rat model was established in order to investigate the effect of miR-18a on cardiomyocyte autophagy and senescence in AMI and the underlying mechanism. In the present study, an AMI model was induced by ligating the anterior descending branch of left coronary artery in Wistar rats. Dual-luciferase reporter gene assay was introduced for exploration on the relationship between miR-18a and brain derived neurotrophic factor ([[BDNF]]). The gain- and loss-of-function experiments were performed to elucidate miR-18a and [[BDNF]] effects on cell autophagy and senescence in AMI by transfecting hypoxia-exposed H9c2 cells with miR-18a inhibitor or mimic, siRNA against [[BDNF]], or hypoxia-exposed H9c2 cell treatment with an agonist of the Akt/mTOR axis (LM22B-10). Upregulation of miR-18a was found in AMI, while downregulation was present in [[BDNF]] to activate the Akt/mTOR axis. Compared with the miR-18a inhibitor group, the expression of p-Akt and p-mTOR increased and the number of senescent cells increased in the miR-18a inhibitor   LM22B-10 group, and the expression of Beclin1, LC3-II, p62 decreased and autophagy decreased (all [i]p[/i] < 0.05). Furthermore, this could be rescued by knocking down [[BDNF]] or Akt/mTOR axis activation by LM22B-10. All in all, downregulation of miR-18a could promote [[BDNF]] expression, which offers protection against AMI by inactivating the Akt/mTOR axis, highlighting a promising therapeutic strategy for AMI treatment.

|keywords=* Acute myocardial infarction
* Akt/mTOR axis
* Autophagy
* Brain derived neurotrophic factor
* MicroRNA-18a
* Senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509849
}}
{{medline-entry
|title=Exercise enhances the expression of brain-derived neurotrophic factor in the hippocampus accompanied by epigenetic alterations in senescence-accelerated mice prone 8.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31108130
|abstract=Exercise increases the expression of brain-derived neurotrophic factor ([[BDNF]]) in the hippocampus and beneficially contributes to cognitive function and is accompanied by epigenetic changes. Specifically, the activity levels of histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate histone acetylation and modulate gene transcription. The objective of the present study was to assess the effect of an exercise regimen over a long period on the expression of [[BDNF]], tropomyosin receptor kinase B (TrkB) and p75, and the activity of HATs and HDACs in the degenerative hippocampus. We used senescence-accelerated mice (SAM), and specifically, 3-month-old SAM resistant 1 (SAMR1) and SAM prone 8 (SAMP8) strains. Mice were distributed into four groups based on accelerated senescence and exercise status. Mice in the exercise groups exercised on a treadmill for 45 min a day, 3 days a week, for 6 months. Exercise significantly increased [[BDNF]] expression and decreased the expression of p75 in both SAMR1 and SAMP8. In addition, aging decreased HAT activity, whereas exercise decreased HDAC activity and increased the activity ratio of HAT to HDAC (HAT/HDAC). Therefore, the present study revealed that despite accelerated senescence, exercise up-regulated the expression of [[BDNF]] along with decreased the expression of p75, a receptor involved in apoptotic signaling. Furthermore, exercise increased HAT/HDAC, which might beneficially contribute to the transcriptional regulation for degenerative changes in the hippocampus.
|mesh-terms=* Aging
* Animals
* Brain-Derived Neurotrophic Factor
* Cognition
* Epigenesis, Genetic
* Gene Expression Regulation
* Hippocampus
* Histone Acetyltransferases
* Histone Deacetylases
* Male
* Membrane Glycoproteins
* Mice
* Physical Conditioning, Animal
* Protein-Tyrosine Kinases
* Receptor, Nerve Growth Factor
|keywords=* Aging
* Epigenetics
* Exercise
* Hippocampus
* Neurotrophin
|full-text-url=https://sci-hub.do/10.1016/j.neulet.2019.05.031
}}
{{medline-entry
|title=Melatonin alleviates cognition impairment by antagonizing brain insulin resistance in aged rats fed a high-fat diet.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31050371
|abstract=Brain insulin resistance, induced by neuroinflammation and oxidative stress, contributes to neurodegeneration, that is, processes that are associated with Aβ accumulation and TAU hyperphosphorylation. Here, we tested the effect of chronic administration of melatonin (MLT) on brain insulin resistance and cognition deficits caused by a high-fat diet (HFD) in aged rats. Results showed that MLT supplementation attenuated peripheral insulin resistance and lowered hippocampal oxidative stress levels. Activated microglia and astrocytes and hippocampal levels of [[TNF]]-α in HFD-fed rats were reduced by MLT treatment. Melatonin also prevented HFD-induced increases in beta-amyloid (Aβ) accumulation and TAU phosphorylation in the hippocampus. In addition, impairments of brain insulin signaling elicited by long-term HFD were restored by MLT treatment, as confirmed by ex vivo insulin stimulation. Importantly, MLT reversed HFD-induced cognitive decline as measured by a water maze test, normalized hippocampal LTP and restored CREB activity and [[BDNF]] levels as well as cholinergic neuronal activity in the hippocampus. Collectively, these findings indicate that MLT may exhibit substantial protective effects on cognition, via restoration of brain insulin signaling.
|mesh-terms=* Aging
* Animals
* Cholinergic Neurons
* Cognitive Dysfunction
* Dietary Fats
* Female
* Hippocampus
* Insulin Resistance
* Maze Learning
* Melatonin
* Oxidative Stress
* Rats
* Rats, Sprague-Dawley
* Tumor Necrosis Factor-alpha
|keywords=* TAU phosphorylation
* amyloid-β
* brain insulin resistance
* cognition impairment
* melatonin
* neuroinflammation
* oxidative stress
|full-text-url=https://sci-hub.do/10.1111/jpi.12584
}}
{{medline-entry
|title=Gross Motor Skills Training Leads to Increased Brain-Derived Neurotrophic Factor Levels in Healthy Older Adults: A Pilot Study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31031639
|abstract=Exercise is recognized as a promising approach to counteract aging-associated declines in cognitive functions. However, the exact molecular pathways involved remain unclear. Aerobic training interventions and improvements in peak oxygen uptake (VO peak) have been associated with increases in the peripheral concentration of brain-derived neurotrophic factor ([[BDNF]]) and better cognitive performances. However, other training interventions such as resistance training and gross motor skills programs were also linked with improvements in cognitive functions. Thus far, few studies have compared different types of physical exercise training protocols and their impact on [[BDNF]] concentrations, especially in participants over 60 years old. The main objective of this study was to compare the effects of three exercise protocols on plasma [[BDNF]] concentrations at rest in healthy older adults. Thirty-four older adults were randomized into three interventions: (1) lower body strength and aerobic training (LBS-A), (2) upper body strength and aerobic training (UBS-A), or (3) gross motor activities (GMA). All interventions were composed of 3 weekly sessions over a period of 8 weeks. Physical, biochemical, and cognitive assessments were performed pre and post-intervention. All interventions resulted in improved cognitive functions but the GMA intervention induced a larger increase in plasma [[BDNF]] concentrations than LBS-A. No correlation was observed between changes in [[BDNF]] concentrations and cognitive performances. These findings suggest that a program of GMA could lead to enhancements in plasma [[BDNF]] concentrations. Moreover, cognition improvement could occur without concomitant detectable changes in [[BDNF]], which highlights the multifactorial nature of the exercise-cognition relationship in older adults.

|keywords=* aging
* biomarkers
* cognition
* exercise
* fitness
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473056
}}
{{medline-entry
|title=Dysregulation of the SNARE-binding protein Munc18-1 impairs [[BDNF]] secretion and synaptic neurotransmission: a novel interventional target to protect the aging brain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31041658
|abstract=Brain-derived neurotrophic factor ([[BDNF]]) has a central role in maintaining and strengthening neuronal connections and to stimulate neurogenesis in the adult brain. Decreased levels of [[BDNF]] in the aging brain are thought to usher cognitive impairment. [[BDNF]] is stored in dense core vesicles and released through exocytosis from the neurites. The exact mechanism for the regulation of [[BDNF]] secretion is not well understood. Munc18-1 (STXBP1) was found to be essential for the exocytosis of synaptic vesicles, but its involvement in [[BDNF]] secretion is not known. Interestingly, neurons lacking munc18-1 undergo severe degeneration in knock-out mice. Here, we report the effects of [[BDNF]] treatment on the presynaptic terminal using munc18-1-deficient neurons. Reduced expression of munc18-1 in heterozygous ( /-) neurons diminishes synaptic transmitter release, as tested here on individual synaptic connections with FM1-43 fluorescence imaging. Transduction of cultured neurons with [[BDNF]] markedly increased [[BDNF]] secretion in wild-type but was less effective in munc18-1  /- cells. In turn, [[BDNF]] enhanced synaptic functions and restored the severe synaptic dysfunction induced by munc18-1 deficiency. The role of munc18-1 in the synaptic effect of [[BDNF]] is highlighted by the finding that [[BDNF]] upregulated the expression of munc18-1 in neurons, consistent with enhanced synaptic functions. Accordingly, this is the first evidence showing the functional effect of [[BDNF]] in munc18-1 deficient synapses and about the direct role of munc18-1 in the regulation of [[BDNF]] secretion. We propose a molecular model of [[BDNF]] secretion and discuss its potential as therapeutic target to prevent cognitive decline in the elderly.
|mesh-terms=* Aging
* Animals
* Brain
* Brain-Derived Neurotrophic Factor
* Cognitive Dysfunction
* Humans
* Mice
* Mice, Knockout
* Munc18 Proteins
* Protein Binding
* SNARE Proteins
* Sensitivity and Specificity
* Synaptic Transmission
* Synaptic Vesicles
|keywords=* BDNF (brain-derived neurotrophic factor) secretion
* Brain aging and dementia
* FM 1-43 fluorescence microscopy
* Neurotransmission
* Synaptic vesicle recycling
* munc18-1
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544690
}}
{{medline-entry
|title=Frailty biomarkers in humans and rodents: Current approaches and future advances.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31002925
|abstract=Even though they would have great benefit across research and clinical fields, currently there are no accepted biomarkers of frailty. Cross-sectional studies in humans have identified promising candidates including inflammatory markers such as IL-6, immune markers such as WBC count, clinical markers such as albumin, endocrine markers such as vitamin D, oxidative stress markers such as isoprostanes, proteins such as [[BDNF]] and epigenetic markers such as DNA methylation, but there are limitations to the current state of the research. Future approaches to the identification of frailty biomarkers should include longitudinal studies, studies using animal models of frailty, studies incorporating novel biomarkers combined into composite panels, and studies investigating sex differences and potential overlap between markers of biological age and frailty.
|mesh-terms=* Aging
* Animals
* Biomarkers
* Brain-Derived Neurotrophic Factor
* DNA Methylation
* Epigenesis, Genetic
* Female
* Frailty
* Humans
* Inflammation Mediators
* Interleukin-6
* Male
* Mice
* Rats
|keywords=* Aging
* Animal models
* Biological age
* Deficit accumulation
* Epigenetics
* Sex differences
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581034
}}
{{medline-entry
|title=Pregnancies alters spine number in cortical and subcortical limbic brain regions of old rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30958589
|abstract=Pregnancy is a complex process, involving a number of hormones and trophic factors, many of which are formed in the placenta. Several of these trophic factors have an effect at the neuronal level, such as [[BDNF]]. Consequently, recent reports have shown that exposure to these hormones (estrogen and progesterone) and trophic factors such as [[BDNF]] exert a neuroprotective effect. Here, we study the effect of the number of pregnancies on dendritic morphology of aged female rats (18 months of age). Rats of the 18-month-old Sprague Dawley strain with zero, one, two, and three gestations were evaluated for locomotor activity, and Golgi-Cox stain was performed to evaluate the dendritic morphology parameters, the number of dendritic spines, total dendritic length, and branching order number. Adult nulliparous rats (3 months of age) were used as another control group. Adult nulliparous and aging rats with two pregnancies showed an increase in locomotor activity. Adult nulliparous showed an increase in the dendritic spine number compared to old nulliparous rats in both layers of the PFC, the DG, and NAcc. Old rats with two and three pregnancies also showed an increase in the number of dendritic spines compared to old nulliparous rats in layers 3 and 5 of the PFC and in the [[CA1]]. Aging animals with one pregnancy also showed an increase in dendritic length compared to old nulliparous rats in the [[CA1]]. Our results clearly suggest that two and three pregnancies increase the dendritic spines number in the PFC and [[CA1]] of aged female rats.
|mesh-terms=* Animals
* Brain
* Dendritic Spines
* Female
* Parity
* Pregnancy
* Rats
* Rats, Sprague-Dawley
|keywords=* aging
* female rats
* hippocampus
* prefrontal cortex
* pregnancies
|full-text-url=https://sci-hub.do/10.1002/syn.22100
}}
{{medline-entry
|title=TrkB Activation during a Critical Period Mimics the Protective Effects of Early Visual Experience on Perception and the Stability of Receptive Fields in Adult Superior Colliculus.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30940716
|abstract=During a critical period in development, spontaneous and evoked retinal activity shape visual pathways in an adaptive fashion. Interestingly, spontaneous activity is sufficient for spatial refinement of visual receptive fields (RFs) in superior colliculus (SC) and visual cortex (V1), but early visual experience is necessary to maintain inhibitory synapses and stabilize RFs in adulthood (Carrasco et al., 2005, 2011; Carrasco and Pallas, 2006; Balmer and Pallas, 2015a). In V1, [[BDNF]] and its high-affinity receptor TrkB are important for development of visual acuity, inhibition, and regulation of the critical period for ocular dominance plasticity (Hanover et al., 1999; Huang et al., 1999; Gianfranceschi et al., 2003). To examine the generality of this signaling pathway for visual system plasticity, the present study examined the role of TrkB signaling during the critical period for RF refinement in SC. Activating TrkB receptors during the critical period (P33-P40) in dark reared subjects produced normally refined RFs, and blocking TrkB receptors in light-exposed animals resulted in enlarged adult RFs like those in dark reared animals. We also report here that deprivation- or TrkB blockade-induced RF enlargement in adulthood impaired fear responses to looming overhead stimuli and negatively impacted visual acuity. Thus, early TrkB activation is both necessary and sufficient to maintain visual RF refinement, robust looming responses, and visual acuity in adulthood. These findings suggest a common signaling pathway exists for the maturation of inhibition between V1 and SC.  Receptive field refinement in superior colliculus differs from more commonly studied examples of critical period plasticity in visual pathways in that it does not require visual experience to occur; rather, spontaneous activity is sufficient. Maintenance of refinement beyond puberty requires a brief, early exposure to light to stabilize the lateral inhibition that shapes receptive fields. We find that TrkB activation during a critical period can substitute for visual experience in maintaining receptive field refinement into adulthood, and that this maintenance is beneficial to visual survival behaviors. Thus, as in some other types of plasticity, TrkB signaling plays a crucial role in receptive field refinement.
|mesh-terms=* Aging
* Animals
* Azepines
* Benzamides
* Cricetinae
* Critical Period, Psychological
* Darkness
* Fear
* Female
* Flavones
* Male
* Maze Learning
* Membrane Glycoproteins
* Mesocricetus
* Mice
* Mice, Inbred C57BL
* Phosphorylation
* Photic Stimulation
* Protein Processing, Post-Translational
* Protein-Tyrosine Kinases
* Sensory Deprivation
* Superior Colliculi
* Visual Perception
|keywords=* adult plasticity
* inhibitory plasticity
* retinotectal
* sensory deprivation
* synaptic plasticity
* visual development
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554622
}}
{{medline-entry
|title=Ageing of the somatosensory system at the periphery: age-related changes in cutaneous mechanoreceptors.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30924930
|abstract=Decline of tactile sensation associated with ageing depends on modifications in skin and both central and peripheral nervous systems. At present, age-related changes in the periphery of the somatosensory system, particularly concerning the effects on mechanoreceptors, remain unknown. Here we used immunohistochemistry to analyse the age-dependent changes in Meissner's and Pacinian corpuscles as well as in Merkel cell-neurite complexes. Moreover, variations in the neurotrophic TrkB-[[BDNF]] system and the mechanoprotein Piezo2 (involved in maintenance of cutaneous mechanoreceptors and light touch, respectively) were evaluated. The number of Meissner's corpuscles and Merkel cells decreased progressively with ageing. Meissner's corpuscles were smaller, rounded in morphology and located deeper in the dermis, and signs of corpuscular denervation were found in the oldest subjects. Pacinian corpuscles generally showed no relevant age-related alterations. Reduced expression of Piezo2 in the axon of Meissner's corpuscles and in Merkel cells was observed in old subjects, as well was a decline in the [[BDNF]]-TrkB neurotrophic system. This study demonstrates that cutaneous Meissner's corpuscles and Merkel cell-neurite complexes (and less evidently Pacinian corpuscles) undergo morphological and size changes during the ageing process, as well as a reduction in terms of density. Furthermore, the mechanoprotein Piezo2 and the neurotrophic TrkB-[[BDNF]] system are reduced in aged corpuscles. Taken together, these alterations might explain part of the impairment of the somatosensory system associated with ageing.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Female
* Fingers
* Humans
* Male
* Mechanoreceptors
* Merkel Cells
* Middle Aged
* Pacinian Corpuscles
* Skin
* Touch
* Young Adult
|keywords=* BDNF-TrkB system
* Piezo2
* ageing
* glabrous skin innervation
* human
* sensory corpuscles
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539748
}}
{{medline-entry
|title=Hydrophilic Glycoproteins of an Edible Green Alga [i]Capsosiphon fulvescens[/i] Prevent Aging-Induced Spatial Memory Impairment by Suppressing GSK-3β-Mediated ER Stress in Dorsal Hippocampus.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30875947
|abstract=Endoplasmic reticulum (ER) stress is involved in various neurodegenerative disorders. We previously found that [i]Capsosiphon fulvescens[/i] ([i]C. fulvescens[/i]) crude proteins enhance spatial memory by increasing the expression of brain-derived neurotrophic factor ([[BDNF]]) in rat dorsal hippocampus. The present study investigated whether the chronic oral administration of hydrophilic [i]C. fulvescens[/i] glycoproteins (Cf-hGP) reduces aging-induced cognitive dysfunction by regulating ER stress in the dorsal hippocampus. The oral administration of Cf-hGP (15 mg/kg/day) for four weeks attenuated the aging-induced increase in ER stress response protein glucose-regulated protein 78 (GRP78) in the synaptosome of the dorsal hippocampus; this was attenuated by the function-blocking anti-[[BDNF]] antibody (1 μg/μL) and a matrix metallopeptidase 9 inhibitor 1 (5 μM). Aging-induced GRP78 expression was associated with glycogen synthase kinase-3 beta (GSK-3β) (Tyr216)-mediated c-Jun N-terminal kinase phosphorylation, which was downregulated upon Cf-hGP administration. The Cf-hGP-induced increase in GSK-3β (Ser9) phosphorylation was downregulated by inhibiting tyrosine receptor kinase B and extracellular signal-regulated kinase (ERK)1/2 with cyclotraxin-B (200 nM) and SL327 (10 μM), respectively. Cf-hGP administration or the inhibition of ER stress with salubrinal (1 mg/kg, i.p.) significantly decreased aging-induced spatial memory impairment. These findings suggest that the activation of the synaptosomal [[BDNF]]-ERK1/2 signaling in the dorsal hippocampus by Cf-hGP attenuates age-dependent ER stress-induced cognitive dysfunction.
|mesh-terms=* Animals
* Brain-Derived Neurotrophic Factor
* Chlorophyta
* Cognitive Aging
* Cognitive Dysfunction
* Endoplasmic Reticulum Stress
* Glycogen Synthase Kinase 3 beta
* Glycoproteins
* HSP70 Heat-Shock Proteins
* Hippocampus
* MAP Kinase Kinase 4
* MAP Kinase Signaling System
* Male
* Matrix Metalloproteinase 9
* Membrane Proteins
* Neuroprotective Agents
* Rats
* Rats, Sprague-Dawley
* Signal Transduction
* Spatial Memory
|keywords=* Capsosiphon fulvescens
* aging
* cognitive dysfunction
* endoplasmic reticulum stress
* glycoproteins
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470841
}}
{{medline-entry
|title=β-Alanine supplementation reduces anxiety and increases neurotrophin expression in both young and older rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30803507
|abstract=The effect of 30 days of β-alanine supplementation (100 mg/kg) on behavioral response and expression of brain-derived neurotrophic factor ([[BDNF]]), neuropeptide Y ([[NPY]]), and markers of inflammation was examined in both young (4 months) and older (14 months) rats. We hypothesized that animals fed β-alanine would experience reduced inflammation and an enhanced neurotrophin and behavioral response. Animals were assigned to either a control group, in which young or older rats were fed regular chow and water, or a β-alanine group, in which rats were fed regular chow and provided β-alanine in their water. Behavior measures were conducted following the 30-day supplementation period, which included spatial learning, memory, and an anxiety index. Hippocampal expressions of [[BDNF]], [[NPY]], glial fibrillary acidic protein, nuclear factor-κB p50 and p65 subunits, tumor necrosis factor-α, and cyclooxygenase-2 were also analyzed. Learning ability was reduced (P = .001) and anxiety index was higher (P = .001) in older compared to young rats. Similarly, [[BDNF]] and [[NPY]] expressions were reduced and all inflammatory markers were elevated (P < .05) in the older animals. β-Alanine increased [[BDNF]] expressions in the cornu ammonis area 1 (P = .003) and 3 (P < .001) subregions of the hippocampus. [[BDNF]] expression for younger rats in the β-alanine group was also significantly greater than younger rats in the control group in cornu ammonis area 3. Learning for young animals fed β-alanine was significantly better than all other groups. Significant reductions in anxiety were noted in both older and younger rats fed β-alanine compared to age-matched controls. Results indicated that β-alanine ingestion in both young and older rats was effective in attenuating anxiety and augmenting [[BDNF]] expression in the hippocampus.
|mesh-terms=* Animals
* Anxiety
* Behavior, Animal
* Brain-Derived Neurotrophic Factor
* Dietary Supplements
* Male
* Nerve Growth Factors
* Rats
* Rats, Sprague-Dawley
* Signal Transduction
* beta-Alanine
|keywords=* Aging
* Anxiety
* BDNF
* Carnosine
* Learning
|full-text-url=https://sci-hub.do/10.1016/j.nutres.2018.11.001
}}
{{medline-entry
|title=Structural and molecular correlates of cognitive aging in the rat.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30765864
|abstract=Aging is associated with cognitive decline. Herein, we studied a large cohort of old age and young adult male rats and confirmed that, as a group, old  rats display poorer spatial learning and behavioral flexibility than younger adults. Surprisingly, when animals were clustered as good and bad performers, our data revealed that while in younger animals better cognitive performance was associated with longer dendritic trees and increased levels of synaptic markers in the hippocampus and prefrontal cortex, the opposite was found in the older group, in which better performance was associated with shorter dendrites and lower levels of synaptic markers. Additionally, in old, but not young individuals, worse performance correlated with increased levels of [[BDNF]] and the autophagy substrate p62, but decreased levels of the autophagy complex protein LC3. In summary, while for younger individuals "bigger is better", "smaller is better" is a more appropriate aphorism for older subjects.
|mesh-terms=* Animals
* Autophagy
* Brain-Derived Neurotrophic Factor
* Cognitive Aging
* Cohort Studies
* Male
* Neurons
* Rats
* Rats, Wistar
* Synapses

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376121
}}
{{medline-entry
|title=Reduction of [[BDNF]] results in GABAergic neuroplasticity dysfunction and contributes to late-life anxiety disorder.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30714802
|abstract=The GABAergic neuroplasticity dysfunction (GND) has been proposed as a distinct pathology for late-life anxiety disorder (LLAD). Brain-derived neurotrophic factor ([[BDNF]]) is a critical signaling molecule that regulates the GABAergic neuroplasticity. This research was designed to explore our hypothesis that the reduction of [[BDNF]] along with aging could induce GND, which might contribute to LLAD, and application of exogenous [[BDNF]] might reverse LLAD by restoring the GABAergic neuroplasticity. We focused on the hippocampus because it is the neural core of mood regulation and can be affected by aging. Compared to young mice, [[BDNF]] messenger RNA (mRNA) and protein levels and those core neuroplasticity factors (neurotransmitter γ-aminobutyric acid [GABA] level, GABAA-R α2 and α5 subunits expression and GABA  neurons) in hippocampus markedly decreased with anxiety-like behavior in aged mice. Knocking down [[BDNF]] mRNA in aged mice resulted in further dysfunction of GABAergic neuroplasticity and higher anxiety phenotype. Inversely, chronic exogenous [[BDNF]] treatment attenuated anxiety-like behavior, improved the cognitive function, and increased the neuroplasticity factors. We demonstrated that the basic function of [[BDNF]] in hippocampus was negatively correlated with GND and anxiety-like behavior of aged mice. These results provided evidence of a causal relationship between the reduced [[BDNF]] function in hippocampus and the anxiety susceptibility of aged mice. Gene knockdown mice model indicates the mechanism of low [[BDNF]] function in LLAD, particularly affecting GABA neurons, therefore bridging the neurotrophic factor and GABAergic neuroplasticity hypotheses of LLAD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
|mesh-terms=* Aging
* Animals
* Anxiety Disorders
* Brain-Derived Neurotrophic Factor
* GABAergic Neurons
* Gene Knockdown Techniques
* Hippocampus
* Male
* Mice
* Neuronal Plasticity
* RNA, Messenger
* Receptors, GABA-A

|full-text-url=https://sci-hub.do/10.1037/bne0000301
}}
{{medline-entry
|title=The Role of Enhanced Cognition to Counteract Detrimental Effects of Prolonged Bed Rest: Current Evidence and Perspectives.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30728781
|abstract=Prolonged periods of physical inactivity or bed rest can lead to a significant decline of functional and cognitive functions. Different kinds of countermeasures (e.g., centrifugation, nutritional, and aerobic interventions) have been developed to attempt to mitigate negative effects related to bed rest confinement. The aim of this report is to provide an overview of the current evidence related to the effectiveness of computerized cognitive training (CCT) intervention during a period of complete physical inactivity in older adults. CCT, using a virtual maze navigation task, appears to be effective and has long-lasting benefits (up to 1.5 years after the study). Moreover, enhanced cognition (executive control) reduces decline in the ability to perform complex motor-cognitive dual-tasks after prolonged period of bed rest. It has been demonstrated that CCT administration in older adults also prevents bed rest stress-related physiological changes [these groups showed minimal changes in vascular function and an unchanged level of brain-derived neurotrophic factor ([[BDNF]])] while control subjects showed decreased peripheral vascularization and increased plasma level of the neurotrophin [[BDNF]] during a 14-day bed rest. In addition, the effects of CCT are evident also from the brain electrocortical findings: CCT group revealed a decreased power in lower delta and theta bands while significant increases in the same EEG spectral bands power were found in control subjects. If we consider an increase of power in delta band as a marker of cortical aging, then the lack of shift of EEG power to lower band indicates a preventive role of CCT on the cortical level during physiological deconditioning induced by 2-week bed rest immobilization. However, replication on a larger sample is required to confirm the observed findings. Applications derived from these findings could be appropriate for implementation of hospital treatment for bed ridden patients as well as for fall prevention programs.

|keywords=* aging
* cognitive training
* falls prevention
* geriatrics
* non-pharmacological countermeasures
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351441
}}
{{medline-entry
|title=A candidate gene study of risk for dementia in older, postmenopausal women: Results from the Women's Health Initiative Memory Study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30706571
|abstract=While a number of single nucleotide polymorphisms (SNPs) associated with Alzheimer's disease (AD) or cognitive impairment have been identified, independent replications remain the only way to validate proposed signals. We investigated SNPs in candidate genes associated with either cognitive impairment or AD pathogenesis and their relationships with probable dementia (PD) in the Women's Health Initiative Memory Study (WHIMS). We analyzed 96 SNPs across five genes ([[APOE]]/[[TOMM40]], [[BDNF]], [[COMT]], [[SORL1]], and KIBRA) in 2857 women (ages ≥65) from the WHIMS randomized trials of hormone therapy using a custom Illumina GoldenGate assay; 19% of the sample were MCI (N = 165) or PD (N = 387), and the remaining 81% were free of cognitive impairment. SNP associations were evaluated for PD in non-Hispanic whites adjusting for age and HT using logistic regression under an additive genetic model. One SNP (rs157582), located in the [[TOMM40]] gene nearby [[APOE]], was associated with the PD phenotype based on a P value accounting for multiple comparisons. An additional 12 SNPs were associated with the PD phenotype at P ≤ 0.05 ([[APOE]]: rs405509, rs439401; [[TOMM40]]: rs8106922, and KIBRA: rs4320284, rs11740112, rs10040267, rs13171394, rs6555802, rs2241368, rs244904, rs6555805, and rs10475878). Results of the sensitivity analyes excluding MCI were similar, with addition of [[COMT]] rs737865 and [[BDNF]] rs1491850 (P ≤ 0.05). Our results in older women provide supporting evidence that the [[APOE]]/[[TOMM40]] genes confer dementia risk and extend these findings to [[COMT]], [[BDNF]], and KIBRA. Our findings may lead to a better understanding of the role these genes play in cognition and cognitive impairment.
|mesh-terms=* Aged
* Alzheimer Disease
* Apolipoproteins E
* Brain-Derived Neurotrophic Factor
* Catechol O-Methyltransferase
* Cognitive Dysfunction
* Dementia
* Female
* Genetic Predisposition to Disease
* Humans
* Intracellular Signaling Peptides and Proteins
* LDL-Receptor Related Proteins
* Membrane Transport Proteins
* Middle Aged
* Polymorphism, Single Nucleotide
* Postmenopause
* Women's Health
|keywords=* AD
* Alzheimer's disease
* MCI
* aging
* hormone therapy
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6608707
}}
{{medline-entry
|title=The TrkB-T1 receptor mediates [[BDNF]]-induced migration of aged cardiac microvascular endothelial cells by recruiting Willin.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30667167
|abstract=The mechanism of age-related decline in the angiogenic potential of the myocardium is not yet fully understood. Our previous report revealed that the aging of cardiac microvascular endothelial cells (CMECs) led to changes in their expression of receptor Trk isoforms: among the three isoforms (TrkB-FL, TrkB-T1 and TrkB-T2), only the truncated TrkB-T1 isoform continued to be expressed in aged CMECs, which led to decreased migration of CMECs in aging hearts. Thus far, how [[BDNF]] induces signalling through the truncated TrkB-T1 isoform in aged CMECs remains unclear. Here, we first demonstrated that aged CMECs utilize [[BDNF]]-TrkB-T1 signalling to recruit Willin as a downstream effector to further activate the Hippo pathway, which then promotes migration. These findings suggest that the aging process shifts the phenotype of aged CMECs that express TrkB-T1 receptors by transducing [[BDNF]] signals via the [[BDNF]]-TrkB-T1-Willin-Hippo pathway and that this change might be an important mechanism and therapeutic target of the dysfunctional cardiac angiogenesis observed in aged hearts.
|mesh-terms=* Animals
* Brain-Derived Neurotrophic Factor
* Cell Movement
* Cells, Cultured
* Cellular Senescence
* Endothelial Cells
* HEK293 Cells
* Humans
* Intracellular Signaling Peptides and Proteins
* Myocytes, Cardiac
* Neovascularization, Physiologic
* Rats
* Receptor, trkB
* Signal Transduction
|keywords=* BDNF-TrkB
* Hippo pathway
* Willin/FRMD6
* cardiac microvascular endothelial cell aging
* migration
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413668
}}
{{medline-entry
|title=Influence of [[BDNF]] Val66Met on the relationship between cardiorespiratory fitness and memory in cognitively normal older adults.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30639507
|abstract=Higher cardiorespiratory fitness has been associated with better cognitive function in older adults; yet, this relationship demonstrates a degree of variability across the older adult population. Thus, it is hypothesised that variation in genetic factors may influence the relationship between fitness and cognitive health. One such genetic factor is the brain-derived neurotrophic factor ([[BDNF]]) Val66Met polymorphism, which has previously been shown to moderate the relationship between self-reported physical activity and memory performance. In this study we aim to investigate the interaction between [[BDNF]] Val66Met polymorphism and objectively-measured cardiorespiratory fitness on performance on tasks assessing verbal and visuospatial memory. Data from ninety-nine cognitively normal men and women aged 60-80 years were used. Fitness was assessed by peak oxygen consumption, and verbal and visuospatial memory were evaluated using well-validated measures. Participants were categorised into: lower-fit Met carriers, higher-fit Met carriers, lower-fit Val/Val, or higher-fit Val/Val. Higher-fit individuals performed better on a task assessing visuospatial memory, compared with lower-fit individuals. Furthermore, an interaction between [[BDNF]] Val66Met and fitness was observed in terms of visuospatial memory performance on a continuous paired associate learning task; whereby lower-fit Met carriers performed 1 standard deviation worse than higher-fit Met carriers. No differences were observed between the higher-fit and lower-fit Val/Val homozygotes. Future intervention studies should evaluate the effect of structured exercise on cognitive health between [[BDNF]] Val66Met carriers and Val/Val homozygotes.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Brain-Derived Neurotrophic Factor
* Cardiorespiratory Fitness
* Cognition
* Female
* Genetic Predisposition to Disease
* Genotype
* Humans
* Male
* Memory, Episodic
* Methionine
* Middle Aged
* Neuropsychological Tests
* Polymorphism, Single Nucleotide
|keywords=* Brain-derived neurotrophic factor Val66Met
* Cardiorespiratory fitness
* Cognition
* Memory
* Physical activity
|full-text-url=https://sci-hub.do/10.1016/j.bbr.2019.01.013
}}
{{medline-entry
|title=Emerging Anti-Aging Strategies - Scientific Basis and Efficacy.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30574426
|abstract=The prevalence of age-related diseases is in an upward trend due to increased life expectancy in humans. Age-related conditions are among the leading causes of morbidity and death worldwide currently. Therefore, there is an urgent need to find apt interventions that slow down aging and reduce or postpone the incidence of debilitating age-related diseases. This review discusses the efficacy of emerging anti-aging approaches for maintaining better health in old age. There are many anti-aging strategies in development, which include procedures such as augmentation of autophagy, elimination of senescent cells, transfusion of plasma from young blood, intermittent fasting, enhancement of adult neurogenesis, physical exercise, antioxidant intake, and stem cell therapy. Multiple pre-clinical studies suggest that administration of autophagy enhancers, senolytic drugs, plasma from young blood, drugs that enhance neurogenesis and [[BDNF]] are promising approaches to sustain normal health during aging and also to postpone age-related neurodegenerative diseases such as Alzheimer's disease. Stem cell therapy has also shown promise for improving regeneration and function of the aged or Alzheimer's disease brain. Several of these approaches are awaiting critical appraisal in clinical trials to determine their long-term efficacy and possible adverse effects. On the other hand, procedures such as intermittent fasting, physical exercise, intake of antioxidants such as resveratrol and curcumin have shown considerable promise for improving function in aging, some of which are ready for large-scale clinical trials, as they are non-invasive, and seem to have minimal side effects. In summary, several approaches are at the forefront of becoming mainstream therapies for combating aging and postponing age-related diseases in the coming years.

|keywords=* Aging
* antioxidants
* astragalus
* autophagy
* curcumin
* intermittent fasting
* neurogenesis
* physical exercise
* plasma transfusion
* resveratrol
* senescent cells
* senolytics
* stem cell therapy
* stem cells
* telomeres
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284760
}}
{{medline-entry
|title=Hypothalamic gene transfer of [[BDNF]] promotes healthy aging in mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30585393
|abstract=The aging process and age-related diseases all involve perturbed energy adaption and impaired ability to cope with adversity. Brain-derived neurotrophic factor ([[BDNF]]) in the hypothalamus plays important role in regulation of energy balance. Our previous studies show that recombinant adeno-associated virus (AAV)-mediated hypothalamic [[BDNF]] gene transfer alleviates obesity, diabetes, and metabolic syndromes in both diet-induced and genetic models. Here we examined the efficacy and safety of a built-in autoregulatory system to control transgene [[BDNF]] expression mimicking the body's natural feedback systems in middle-aged mice. Twelve-month-old mice were treated with either autoregulatory [[BDNF]] vector or yellow fluorescence protein (YFP) control, maintained on normal diet, and monitored for 28 weeks. [[BDNF]] gene transfer prevented the development of aging-associated metabolic declines characterized by: preventing aging-associated weight gain, reducing adiposity, reversing the decline of brown fat activity, increasing adiponectin while reducing leptin and insulin in circulation, improving glucose tolerance, increasing energy expenditure, alleviating hepatic steatosis, and suppressing inflammatory genes in the hypothalamus and adipose tissues. Moreover, [[BDNF]] treatment reduced anxiety-like and depression-like behaviors. These safety and efficacy data provide evidence that hypothalamic [[BDNF]] is a target for promoting healthy aging.
|mesh-terms=* Animals
* Brain-Derived Neurotrophic Factor
* Female
* Healthy Aging
* Hypothalamus
* Mice
* Mice, Inbred C57BL
|keywords=* BDNF
* adipose tissue
* aging
* gene transfer
* hypothalamus
* steatosis
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413658
}}
{{medline-entry
|title=Sex-dependent effect of the [[BDNF]] Val66Met polymorphism on executive functioning and processing speed in older adults: evidence from the health ABC study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30448615
|abstract=Brain-derived neurotrophic factor ([[BDNF]]) Val66Met polymorphism may be an important source of heterogeneity seen in cognitive aging, although the specific relationship between this polymorphism and cognition remains controversial and may depend on the sex of participants. We assessed 2668 older black and white adults and fit linear mixed models to digit symbol substitution test (DSST) performance assessed in years 0 (baseline), 4, 7, and 9 to examine the interaction between sex and [[BDNF]] genotype on the intercept (i.e., estimated baseline DSST) and change in DSST over 9 years, adjusted for covariates. Sex interacted with [[BDNF]] genotype to predict DSST intercept (F[1,1599] = 7.4, p < 0.01) and 9-year change (F[1,1183] = 4.1, p = 0.04) in white participants only. Initially, white male Val/Val carriers had lower DSST scores (37.6, SE = 0.8) in comparison with male Met carriers (difference, -1.7; 95% CI, -3.2 to -0.3) and female Val/Val carriers (difference, -5.6; 95% CI, -6.8 to -4.3). White female Met carriers showed a slower rate of change (annual rate of change = -0.6, SE = 0.1) in comparison with female Val/Val carriers (difference, -0.2; 95% CI, -0.4 to -0.02) and male Met carriers (difference, -0.3; 95% CI, -0.5 to -0.02). Our findings suggest that [[BDNF]] Val66Met and sex should be considered in future endeavors aimed at treating or preventing neurodegenerative disorders.
|mesh-terms=* Aged
* Aging
* Brain-Derived Neurotrophic Factor
* Cognitive Aging
* Cohort Studies
* Executive Function
* Female
* Genotype
* Humans
* Male
* Neurodegenerative Diseases
* Polymorphism, Genetic
* Prospective Studies
* Sex Characteristics
|keywords=* Brain-derived neurotrophic factor
* Cognitive aging
* Epidemiology
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358016
}}
{{medline-entry
|title=Brain-Derived Neurotrophic Factor and Its Associations with Metabolism and Physical Activity in a Latino Sample.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30418087
|abstract=Brain-derived neurotrophic factor ([[BDNF]]) is associated with body weight and other health conditions but remains understudied in the Latino population. The aim of this study was to examine the associations of [[BDNF]] serum levels with body mass index (BMI), physical activity, and the rs6265 nonconservative polymorphism among 349 Latinos aged ≥18 years enrolled in the Arizona Insulin Resistance Registry. Data on physical activity were acquired using a self-reported questionnaire. [[BDNF]] serum levels were measured utilizing a modified ELISA method, and the rs6265 polymorphism was genotyped by the Assay-by-Design service. Two sample t-tests or chi-squared tests were employed to compare demographics and outcomes between physically active and nonactive groups as well as between rs6265 CC and CT TT groups. [[BDNF]] levels and rs6265 polymorphism did not differ significantly between the physically active (N = 195) and nonactive group (N = 154). Participants with the rs6265 polymorphism did not show any significant difference in [[BDNF]] levels or BMI when compared with those with the normal functional variant. Higher [[BDNF]] levels were significantly associated with higher age (r = 0.11, P = 0.04) and higher 2-hr glucose level (r = 0.11, P = 0.04). In this cross-sectional study, the rs6265 polymorphism was not associated with a higher risk of obesity, or lower circulating levels of [[BDNF]]. Thus, the rs6265 polymorphism may have a different impact in Latinos as compared with other previously studied populations.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Aging
* Arizona
* Blood Glucose
* Body Mass Index
* Brain-Derived Neurotrophic Factor
* Cross-Sectional Studies
* Exercise
* Female
* Gene Frequency
* Genotype
* Hispanic Americans
* Humans
* Male
* Metabolism
* Middle Aged
* Polymorphism, Genetic
* Young Adult
|keywords=* BDNF
* Latinos
* metabolism
* physical activity
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484340
}}
{{medline-entry
|title=Exercise training increases cardiac, hepatic and circulating levels of brain-derived neurotrophic factor and irisin in young and aged rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30367793
|abstract=Background The objective of study was to examine the impacts of exercise training on cardiac, hepatic and plasma brain-derived neurotrophic factor ([[BDNF]]) and irisin levels in young and aged rats. Materials and methods Four-month-old (young) and 20-month-old (aged) female rats performed exercise training consisting of voluntary wheel running for 12 weeks. [[BDNF]] and irisin levels were analyzed in the heart, liver and plasma samples by using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Results Cardiac, hepatic and plasma [[BDNF]] levels were lower in the aged sedentary rats, than in the young exercised and aged exercised rats (p < 0.05). Heart, liver and plasma irisin concentrations were lower in the aged sedentary group than in the young sedentary, young exercised and aged exercised groups (p < 0.05) and regular exercise increased irisin levels in all the analyzed tissues when compared to the sedentary counterparts (p < 0.05). Conclusions The current results show that regular exercise improves aging-induced decrease in the cardiac, hepatic and plasma BNDF and irisin levels.
|mesh-terms=* Animals
* Brain-Derived Neurotrophic Factor
* Female
* Fibronectins
* Liver
* Myocardium
* Physical Conditioning, Animal
* Rats
* Rats, Inbred WKY
|keywords=* aging
* brain-derived neurotrophic factor
* exercise
* irisin
* myokines
|full-text-url=https://sci-hub.do/10.1515/hmbci-2018-0053
}}
{{medline-entry
|title=RbAp48 Protein Is a Critical Component of [[GPR158]]/OCN Signaling and Ameliorates Age-Related Memory Loss.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30355501
|abstract=Precisely deciphering the molecular mechanisms of age-related memory loss is crucial to create appropriate therapeutic interventions. We have previously shown that the histone-binding protein RbAp48/Rbbp4 is a molecular determinant of Age-Related Memory Loss. By exploring how this protein regulates the genomic landscape of the hippocampal circuit, we find that RbAp48 controls the expression of [[BDNF]] and [[GPR158]] proteins, both critical components of osteocalcin (OCN) signaling in the mouse hippocampus. We show that inhibition of RbAp48 in the hippocampal formation inhibits OCN's beneficial functions in cognition and causes deficits in discrimination memory. In turn, disruption of OCN/[[GPR158]] signaling leads to the downregulation of RbAp48 protein, mimicking the discrimination memory deficits observed in the aged hippocampus. We also show that activation of the OCN/[[GPR158]] pathway increases the expression of RbAp48 in the aged dentate gyrus and rescues age-related memory loss.
|mesh-terms=* Aging
* Animals
* Conditioning, Psychological
* Dentate Gyrus
* Fear
* HEK293 Cells
* Humans
* Memory
* Memory Disorders
* Mice
* Mice, Inbred C57BL
* Osteocalcin
* Receptors, G-Protein-Coupled
* Retinoblastoma-Binding Protein 4
* Signal Transduction
* Up-Regulation
|keywords=* RbAp48
* aging
* hippocampus
* memory
* osteocalcin
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725275
}}
{{medline-entry
|title=Amygdala subnuclei and healthy cognitive aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30291764
|abstract=Amygdala is a group of nuclei involved in the neural circuits of fear, reward learning, and stress. The main goal of this magnetic resonance imaging (MRI) study was to investigate the relationship between age and the amygdala subnuclei volumes in a large cohort of healthy individuals. Our second goal was to determine effects of the apolipoprotein E ([[APOE]]) and brain-derived neurotrophic factor ([[BDNF]]) polymorphisms on the amygdala structure. One hundred and twenty-six healthy participants (18-85 years old) were recruited for this study. MRI datasets were acquired on a 4.7 T system. Amygdala was manually segmented into five major subdivisions (lateral, basal, accessory basal nuclei, and cortical, and centromedial groups). The [[BDNF]] (methionine and homozygous valine) and [[APOE]] genotypes (ε2, homozygous ε3, and ε4) were obtained using single nucleotide polymorphisms. We found significant nonlinear negative associations between age and the total amygdala and its lateral, basal, and accessory basal nuclei volumes, while the cortical amygdala showed a trend. These age-related associations were found only in males but not in females. Centromedial amygdala did not show any relationship with age. We did not observe any statistically significant effects of [[APOE]] and [[BDNF]] polymorphisms on the amygdala subnuclei volumes. In contrast to [[APOE]] ε2 allele carriers, both older [[APOE]] ε4 and ε3 allele carriers had smaller lateral, basal, accessory basal nuclei volumes compared to their younger counterparts. This study indicates that amygdala subnuclei might be nonuniformly affected by aging and that age-related association might be gender specific.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Amygdala
* Apolipoproteins E
* Brain-Derived Neurotrophic Factor
* Cognitive Aging
* Female
* Healthy Aging
* Humans
* Magnetic Resonance Imaging
* Male
* Middle Aged
* Polymorphism, Single Nucleotide
* Sex Factors
* Young Adult
|keywords=* aging
* amygdala subnuclei
* apolipoprotein E (APOE)
* brain-derived neurotrophic factor (BDNF)
* magnetic resonance imaging
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865708
}}
{{medline-entry
|title=[[BDNF]] trafficking and signaling impairment during early neurodegeneration is prevented by moderate physical activity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30135925
|abstract=Physical exercise can attenuate the effects of aging on the central nervous system by increasing the expression of neurotrophins such as brain-derived neurotrophic factor ([[BDNF]]), which promotes dendritic branching and enhances synaptic machinery, through interaction with its receptor TrkB. TrkB receptors are synthesized in the cell body and are transported to the axonal terminals and anchored to plasma membrane, through SLP1, CRMP2 and Rab27B, associated with [[KIF1B]]. Retrograde trafficking is made by EDH-4 together with dynactin and dynein molecular motors. In the present study it was found that early neurodegeneration is accompanied by decrease in [[BDNF]] signaling, in the absence of hyperphosphorylated tau aggregation, in hippocampus of 11 months old Lewis rats exposed to rotenone. It was also demonstrated that moderate physical activity (treadmill running, during 6 weeks, concomitant to rotenone exposure) prevents the impairment of [[BDNF]] system in aged rats, which may contribute to delay neurodegeneration. In conclusion, decrease in [[BDNF]] and TrkB vesicles occurs before large aggregate-like p-Tau are formed and physical activity applied during early neurodegeneration may be of relevance to prevent [[BDNF]] system decay.

|keywords=* Aging
* Early neurodegeneration
* Hippocampus
* Hyperphosphorylated Tau
* Treadmill running
* TrkB receptor
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084862
}}
{{medline-entry
|title=Walnut diets up-regulate the decreased hippocampal neurogenesis and age-related cognitive dysfunction in d-galactose induced aged rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30101966
|abstract=Recently, dietary intervention has been considered as a prospective strategy in delaying age-related cognitive dysfunction and brain plasticity degeneration. This study explored the effect of walnut diets (6% and 9%, 8 weeks) on cognitive behavior, hippocampal neurogenesis and the neurotrophic signaling pathway in d-galactose (d-gal) model rats. Behavioral tests showed that walnut diets significantly reversed spatial memory loss in the Morris water test, locomotor activity deficiency in an open field test, and a recognition behavior reduction in a novel object recognition task. Immunohistochemistry analysis demonstrated walnut diets significantly increased the hippocampal neurogenesis in d-gal model rats. Moreover, western blot results indicated that walnut diets reserved a d-gal induced decrease of hippocampal pCREB (Ser133) and [[BDNF]] expression, two crucial intracellular molecules involved in hippocampal neurogenesis. These findings confirmed that chronic walnut-rich diets could ameliorate cognitive dysfunction in d-gal model rats, and the up-regulation of neurogenesis, as well as the expression of pCREB and [[BDNF]] in hippocampus, may be one of the molecular and cellular mechanisms underlying these effects.
|mesh-terms=* Aging
* Animals
* Behavior, Animal
* Brain-Derived Neurotrophic Factor
* Cognitive Dysfunction
* Cyclic AMP Response Element-Binding Protein
* Functional Food
* Galactose
* Hippocampus
* Immunohistochemistry
* Juglans
* Neurogenesis
* Neuronal Plasticity
* Neurons
* Nuts
* Phosphorylation
* Protein Processing, Post-Translational
* Random Allocation
* Rats, Sprague-Dawley
* Recognition, Psychology
* Signal Transduction
* Spatial Memory

|full-text-url=https://sci-hub.do/10.1039/c8fo00702k
}}
{{medline-entry
|title=Genetics of stroke recovery: [[BDNF]] val66met polymorphism in stroke recovery and its interaction with aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30118755
|abstract=Stroke leads to long term sensory, motor and cognitive impairments. Most patients experience some degree of spontaneous recovery which is mostly incomplete and varying greatly among individuals. The variation in recovery outcomes has been attributed to numerous factors including lesion size, corticospinal tract integrity, age, gender and race. It is well accepted that genetics play a crucial role in stroke incidence and accumulating evidence suggests that it is also a significant determinant in recovery. Among the number of genes and variations implicated in stroke recovery the val66met single nucleotide polymorphism (SNP) in the [[BDNF]] gene influences post-stroke plasticity in the most significant ways. Val66met is the most well characterized [[BDNF]] SNP and is common (40-50 % in Asian and 25-32% in Caucasian populations) in humans. It reduces activity-dependent [[BDNF]] release, dampens cortical plasticity and is implicated in numerous diseases. Earlier studies on the effects of val66met on stroke outcome and recovery presented primarily a maladaptive role. Novel findings however indicate a much more intricate interaction between val66met and stroke recovery which appears to be influenced by lesion location, post-stroke stage and age. This review will focus on the role of [[BDNF]] and val66met SNP in relation to stroke recovery and try to identify potential pathophysiologic mechanisms involved. The effects of age on val66met associated alterations in plasticity and potential consequences in terms of stroke are also discussed.
|mesh-terms=* Aging
* Brain-Derived Neurotrophic Factor
* Humans
* Neuronal Plasticity
* Polymorphism, Single Nucleotide
* Recovery of Function
* Stroke
|keywords=* BDNF
* Recovery
* Stroke
* val66met
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653673
}}
{{medline-entry
|title=Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30117106
|abstract=Brain-derived neurotrophic factor ([[BDNF]]) is one of the most studied neurotrophins in the healthy and diseased brain. As a result, there is a large body of evidence that associates [[BDNF]] with neuronal maintenance, neuronal survival, plasticity, and neurotransmitter regulation. Patients with psychiatric and neurodegenerative disorders often have reduced [[BDNF]] concentrations in their blood and brain. A current hypothesis suggests that these abnormal [[BDNF]] levels might be due to the chronic inflammatory state of the brain in certain disorders, as neuroinflammation is known to affect several [[BDNF]]-related signaling pathways. Activation of glia cells can induce an increase in the levels of pro- and antiinflammatory cytokines and reactive oxygen species, which can lead to the modulation of neuronal function and neurotoxicity observed in several brain pathologies. Understanding how neuroinflammation is involved in disorders of the brain, especially in the disease onset and progression, can be crucial for the development of new strategies of treatment. Despite the increasing evidence for the involvement of [[BDNF]] and neuroinflammation in brain disorders, there is scarce evidence that addresses the interaction between the neurotrophin and neuroinflammation in psychiatric and neurodegenerative diseases. This review focuses on the effect of acute and chronic inflammation on [[BDNF]] levels in the most common psychiatric and neurodegenerative disorders and aims to shed some light on the possible biological mechanisms that may influence this effect. In addition, this review will address the effect of behavior and pharmacological interventions on [[BDNF]] levels in these disorders.
|mesh-terms=* Aging
* Animals
* Brain
* Brain Diseases
* Brain-Derived Neurotrophic Factor
* Humans
* Inflammation
* Models, Biological
|keywords=* Brain-derived neurotrophic factor
* Neuroinflammation
* Neurological disorders
* Neurotoxicity
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476855
}}
{{medline-entry
|title=Is Objectively Assessed Sedentary Behavior, Physical Activity and Cardiorespiratory Fitness Linked to Brain Plasticity Outcomes in Old Age?
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30077618
|abstract=The aim of this cross-sectional study was to determine the associations of objectively assessed habitual physical activity and physical performance with brain plasticity outcomes and brain-derived neurotrophic factor ([[BDNF]]) levels in cognitively healthy older adults. Physical performance was analyzed based on cardiopulmonary exercise-testing data and accelerometer-based physical activity was analyzed as total activity counts, sedentary time, light physical activity and moderate to vigorous physical activity. Brain plasticity outcomes included magnetic resonance spectroscopy (MRS)-based markers, quantitative imaging-based hippocampal volume and [[BDNF]] serum levels. The association between physical performance and hippocampal volume was strongly influenced by participants' education, sex, age and BMI. Confounder-controlled correlation revealed significant associations of brain plasticity outcomes with physical activity but not with performance. MRS-based adenosine triphosphate to phosphocreatine and glycerophosphocholine to phosphocreatine ratios were significantly associated with accelerometer total activity counts. [[BDNF]] was detrimentally associated with sedentary time but beneficially related to accelerometer total activity counts and moderate to vigorous physical activity. Exceeding the current moderate to vigorous physical activity recommendations led to significantly higher [[BDNF]] levels. Our results indicate that regular physical activity might be beneficial for preserving brain plasticity in higher age. In this study these associations were not mediated significantly by physical performance. Overall physical activity and exceeding current moderate to vigorous physical activity recommendations were positively associated with [[BDNF]]. Sedentary behavior, however, seems to be negatively related to neurotrophic factor bioavailability in the elderly.
|mesh-terms=* Accelerometry
* Aged
* Aging
* Body Mass Index
* Brain
* Brain-Derived Neurotrophic Factor
* Cardiorespiratory Fitness
* Cross-Sectional Studies
* Educational Status
* Endurance Training
* Exercise
* Female
* Health Promotion
* Humans
* Magnetic Resonance Imaging
* Magnetic Resonance Spectroscopy
* Male
* Neuronal Plasticity
* Organ Size
* Sedentary Behavior
|keywords=* aging
* brain volume
* cognitive decline
* cognitive function
* elderly
* neuronal energy reserve
|full-text-url=https://sci-hub.do/10.1016/j.neuroscience.2018.07.050
}}
{{medline-entry
|title=Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30071357
|abstract=Use of the frailty index to measure an accumulation of deficits has been proven a valuable method for identifying elderly people at risk for increased vulnerability, disease, injury, and mortality. However, complementary molecular frailty biomarkers or ideally biomarker panels have not yet been identified. We conducted a systematic search to identify biomarker candidates for a frailty biomarker panel. Gene expression databases were searched (http://genomics.senescence.info/genes including GenAge, AnAge, LongevityMap, CellAge, DrugAge, Digital Aging Atlas) to identify genes regulated in aging, longevity, and age-related diseases with a focus on secreted factors or molecules detectable in body fluids as potential frailty biomarkers. Factors broadly expressed, related to several "hallmark of aging" pathways as well as used or predicted as biomarkers in other disease settings, particularly age-related pathologies, were identified. This set of biomarkers was further expanded according to the expertise and experience of the authors. In the next step, biomarkers were assigned to six "hallmark of aging" pathways, namely (1) inflammation, (2) mitochondria and apoptosis, (3) calcium homeostasis, (4) fibrosis, (5) NMJ (neuromuscular junction) and neurons, (6) cytoskeleton and hormones, or (7) other principles and an extensive literature search was performed for each candidate to explore their potential and priority as frailty biomarkers. A total of 44 markers were evaluated in the seven categories listed above, and 19 were awarded a high priority score, 22 identified as medium priority and three were low priority. In each category high and medium priority markers were identified. Biomarker panels for frailty would be of high value and better than single markers. Based on our search we would propose a core panel of frailty biomarkers consisting of (1) [[CXCL10]] (C-X-C motif chemokine ligand 10), IL-6 (interleukin 6), [[CX3CL1]] (C-X3-C motif chemokine ligand 1), (2) [[GDF15]] (growth differentiation factor 15), [[FNDC5]] (fibronectin type III domain containing 5), vimentin (VIM), (3) regucalcin (RGN/SMP30), calreticulin, (4) [[PLAU]] (plasminogen activator, urokinase), [[AGT]] (angiotensinogen), (5) [[BDNF]] (brain derived neurotrophic factor), progranulin (PGRN), (6) α-klotho (KL), [[FGF23]] (fibroblast growth factor 23), [[FGF21]], leptin (LEP), (7) miRNA (micro Ribonucleic acid) panel (to be further defined), [[AHCY]] (adenosylhomocysteinase) and [[KRT18]] (keratin 18). An expanded panel would also include (1) pentraxin (PTX3), sVCAM/ICAM (soluble vascular cell adhesion molecule 1/Intercellular adhesion molecule 1), defensin α, (2) [[APP]] (amyloid beta precursor protein), LDH (lactate dehydrogenase), (3) [[S100B]] (S100 calcium binding protein B), (4) TGFβ (transforming growth factor beta), PAI-1 (plasminogen activator inhibitor 1), [[TGM2]] (transglutaminase 2), (5) sRAGE (soluble receptor for advanced glycosylation end products), [[HMGB1]] (high mobility group box 1), C3/C1Q (complement factor 3/1Q), ST2 (Interleukin 1 receptor like 1), agrin (AGRN), (6) IGF-1 (insulin-like growth factor 1), resistin (RETN), adiponectin (ADIPOQ), ghrelin (GHRL), growth hormone (GH), (7) microparticle panel (to be further defined), GpnmB (glycoprotein nonmetastatic melanoma protein B) and lactoferrin (LTF). We believe that these predicted panels need to be experimentally explored in animal models and frail cohorts in order to ascertain their diagnostic, prognostic and therapeutic potential.
|mesh-terms=* Aged
* Aging
* Amyloid beta-Peptides
* Amyloid beta-Protein Precursor
* Animals
* Apoptosis
* Biomarkers
* Fibronectins
* Frailty
* Genetic Association Studies
* Growth Differentiation Factor 15
* Humans
* Insulin-Like Growth Factor I
* Interleukin-1 Receptor-Like 1 Protein
* Membrane Glycoproteins
* MicroRNAs
* Signal Transduction
|keywords=* Age-related diseases
* Biomarker panel
* Frailty
* Hallmark of aging pathways
|full-text-url=https://sci-hub.do/10.1016/j.arr.2018.07.004
}}
{{medline-entry
|title=Remodeling of myelinated fibers and internal capillaries in distal peripheral nerves following aerobic exercise in aged rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30024334
|abstract=The aim of this study was to determine whether aerobic exercise (AE) in old age contributes to improving the morphologies of myelinated fibers (MFs) in peripheral nerves as well as capillaries. Furthermore, we investigated whether such processes are associated with complementary activity of brain-derived neurotrophic factor ([[BDNF]]) and vascular endothelial growth factor (VEGF) in the circulating blood and peripheral nerve tissue. Fourteen male Wistar rats (age: 95 wk) were randomly divided into moderate AE ( n = 8) and sedentary (SED; n = 6) groups. Rats in the AE group performed treadmill running for 1 h per day for 2 wk, following which the bilateral tibial nerves of the two groups were removed to examine MF and capillary structure. Levels of [[BDNF]] and VEGF in the serum and peripheral nerves were analyzed via enzyme-linked immunosorbent assay. Myelin thickness, axon diameter, and capillary luminal diameter were significantly larger in the AE group than in the SED group ( P < 0.0001). Levels of serum [[BDNF]] and VEGF were significantly lower and higher, respectively, in the AE group than in the SED group ( P < 0.001). Conversely, [[BDNF]] and VEGF levels in tibial nerve tissue were significantly higher, respectively, and lower in the AE group than in the SED group ( P < 0.001). In conclusion, our study indicates that regular AE induces enlargement of the capillaries and thickens the myelin in aged peripheral nerves, likely via a complementary process involving [[BDNF]] and VEGF. NEW