Редактирование: S100B (раздел)

==Publications==

{{medline-entry
|title=Aging protects rat cortical slices against to oxygen-glucose deprivation induced damage.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32064981
|abstract= In present study, we aimed to clarify effect of aging on the susceptibility of brain tissue to neurodegeneration induced by ischemia.  Damage induced by oxygen-glucose deprivation (OGD) followed by reoxygenation (REO) were compared in cortical slices prepared from young (3 months of age) and aged (22-24 months of age) male Sprague Dawley rats.  After incubation of the slices in an oxygen and glucose containing control condition, 2,3,5-triphenyl tetrazolium chloride (TTC) staining intensity was found significantly high in aged cortical slices. Although thirty minutes incubation of the slices in OGD medium followed by REO (OGD-REO) caused similar decline in TTC staining in young and aged cortical slices, staining intensity was still significantly higher in the slices prepared from aged animals. Thirty minutes of OGD-REO, on the other hand, also caused more increase in lactate dehydrogenase (LDH) leakage from young slices. While water contents of the slices were almost equal under control condition, it was significantly high in young cortical slices after OGD-REO incubations. In contrary to these findings, OGD and REO caused more increases in [[S100B]] output from aged rat cortical slices. [[S100B]] levels in brain regions including the cerebral cortex were also found higher in aged rats.  All these results indicate that, cortical slices prepared from aged male rats are significantly less responsive to [i]in vitro[/i] OGD-REO induced alterations. Since protein [[S100B]] outputs were almost doubled from aged cortical slices, a possible involvement of this enhanced [[S100B]] output seems to be likely.

|keywords=* Aging
* LDH
* S100B
* edema
* oxygen-glucose deprivation
|full-text-url=https://sci-hub.do/10.1080/00207454.2020.1730830
}}
{{medline-entry
|title=Hearing loss through apoptosis of the spiral ganglion neurons in apolipoprotein E knockout mice fed with a western diet.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31948760
|abstract=Age-related hearing loss (ARHL) is a neurodegenerative disease associated with an aged population. ARHL is influenced by biological factors such as aging, sex difference, and atherosclerosis. The mechanisms of ARHL caused by atherosclerosis have not been previously determined in apolipoprotein E knockout (ApoE KO) male mice. To investigate the onset and cause of the hearing loss, ApoE KO male mice were treated with a western diet (ApoE KO-WD) for 16 weeks. The lipid profile, atherosclerotic plaques throughout the aorta, and auditory brainstem response ([[ABR]]) thresholds were measured in the ApoE KO-WD male mice. The expression of S100 calcium-binding protein B ([[S100B]]), a neuronal damage biomarker, was also observed. Reactive oxygen species (ROS) and apoptosis rates were detected in the cochlea of the ApoE KO male mice. Atherosclerotic plaques on the aorta and [[ABR]] thresholds were significantly increased in the ApoE KO-WD male mice at 24 weeks of age. [[ABR]] thresholds had a statistically significant positive correlation with the area of atherosclerotic plaques (r = 0.783, p = 0.013) in male mice at 24 weeks of age. [[S100B]] protein expression and the dihydroethidium (DHE) reaction to ROS in the cochlear spiral ganglion neurons (SGNs) were significantly increased in the ApoE KO and ApoE KO-WD male mice. Cells positive for active caspase-3 and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) in the SGNs were significantly increased in ApoE KO-WD male mice indicating an increased rate of cellular apoptosis. In conclusion, ROS in the SGNs were activated by increased [[S100B]] expression in ApoE KO-WD male mice, and this resulted in an increased apoptosis rate. Thus, hearing loss began at 16 weeks in ApoE KO-WD male mice. Our results suggest that the ApoE KO-WD male mice are a suitable animal model for studying ARHL associated with exacerbated atherosclerosis.
|mesh-terms=* Aging
* Animals
* Apolipoproteins E
* Apoptosis
* Diet, Western
* Disease Models, Animal
* Hearing Loss
* Male
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Neurons
* Spiral Ganglion
|keywords=* Apoptosis
* Atherosclerosis
* Hearing loss
* Reactive oxygen specie
* Spiral ganglion neurons
|full-text-url=https://sci-hub.do/10.1016/j.bbrc.2019.12.100
}}
{{medline-entry
|title=The Role of [[S100B]] in Aerobic Training Efficacy in Older Adults with Mild Vascular Cognitive Impairment: Secondary Analysis of a Randomized Controlled Trial.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31075314
|abstract=Aerobic training improves cognitive and brain outcomes across different populations and neurocognitive disorders of aging, including mild subcortical ischemic vascular cognitive impairment (SIVCI). However, little is known of the underlying mechanisms through which aerobic training exerts its beneficial effects on the brain. Recently, S100 calcium-binding protein B ([[S100B]]) has been proposed as a possible mediator of aerobic training. Thus we conducted a secondary analysis of data collected from the proof-of-concept single-blind randomized controlled trial (NCT01027858) in older adults with mild SIVCI to determine whether the beneficial effects of 6-months, thrice weekly, moderate-intensity aerobic training on cognitive performance is related to changes in [[S100B]] levels. At trial completion, aerobic training decreased circulating levels of [[S100B]] compared with usual care plus education. Furthermore, reduced [[S100B]] levels were associated with improved global cognitive function in those who received the aerobic exercise intervention. Together these findings suggest that [[S100B]] is a promising target mediating the beneficial effects of moderate-intensity aerobic training on brain health in older adults with mild SIVCI.
|mesh-terms=* Aged
* Aged, 80 and over
* Biomarkers
* Cognitive Dysfunction
* Exercise
* Exercise Therapy
* Female
* Follow-Up Studies
* Humans
* Male
* Neuropsychological Tests
* S100 Calcium Binding Protein beta Subunit
* Single-Blind Method
* Treatment Outcome
|keywords=* S100B
* aging
* cognition
* exercise
* randomized controlled trial
* vascular cognitive impairment
|full-text-url=https://sci-hub.do/10.1016/j.neuroscience.2019.04.052
}}
{{medline-entry
|title=Changes in mechanoreceptors in rabbits' anterior cruciate ligaments with age.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30927131
|abstract=At present, a few studies have been done on the changes in the distribution, morphology and quantity of mechanoreceptors in anterior cruciate ligament (ACL) with age. In this study, we observed the changes in mechanoreceptors of healthy rabbits' ACL with age. We found that rabbits' ACLs contained 5 kinds of mechanoreceptors including Ruffini corpuscles, Pacinian corpuscles, Golgitendon bodies, free nerve endings and atypical mechanoreceptors. In each ACL, free nerve endings were the most followed by Ruffini corpuscles, Pacinian corpuscles, Golgitendon bodies and atypical mechanoreceptors in the younger than one-old rabbits. Most of the mechanoreceptors were distributed in the synovium near the attachment points of ACL with the femur and tibia. The total quantity of mechanoreceptors were the most in the 3- and 6-month groups, but did not show a significant difference between the two group (P > 0.05). However, there were significant differences in the total quantity of mechanoreceptors between other groups (all P < 0.05). RT-PCR indicated that [[NEFM]] and [[S100B]] levels increased with age, and reached a peak in the 1-year group with significant differences as compared to other groups. [[NEFM]] and [[S100B]] levels were the second in 6-month and 2-year groups and the lowest in the 1-week group. We can conclude that in rabbits' ACLs, free nerve endings are the most common, followed by Ruffini corpuscles, Pacinian corpuscles and Golgitendon bodies. The total quantity of mechanoreceptors reaches a peak in 3 months, while [[NEFM]] and [[S100B]] reach a peak in 1 year.
|mesh-terms=* Aging
* Animals
* Anterior Cruciate Ligament
* Disease Models, Animal
* Humans
* Mechanoreceptors
* Neurofilament Proteins
* Rabbits
* S100 Calcium Binding Protein beta Subunit
* Tibia
|keywords=* Anterior cruciate ligament
* Knee joint
* Mechanoreceptor
* Proprioception
|full-text-url=https://sci-hub.do/10.1007/s10735-019-09820-4
}}
{{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=DNA methylation analysis on purified neurons and glia dissects age and Alzheimer's disease-specific changes in the human cortex.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30045751
|abstract=Epigenome-wide association studies (EWAS) based on human brain samples allow a deep and direct understanding of epigenetic dysregulation in Alzheimer's disease (AD). However, strong variation of cell-type proportions across brain tissue samples represents a significant source of data noise. Here, we report the first EWAS based on sorted neuronal and non-neuronal (mostly glia) nuclei from postmortem human brain tissues. We show that cell sorting strongly enhances the robust detection of disease-related DNA methylation changes even in a relatively small cohort. We identify numerous genes with cell-type-specific methylation signatures and document differential methylation dynamics associated with aging specifically in neurons such as [[CLU]], [[SYNJ2]] and [[NCOR2]] or in glia [[RAI1]],CXXC5 and [[INPP5A]]. Further, we found neuron or glia-specific associations with AD Braak stage progression at genes such as [[MCF2L]], [[ANK1]], [[MAP2]], [[LRRC8B]], [[STK32C]] and [[S100B]]. A comparison of our study with previous tissue-based EWAS validates multiple AD-associated DNA methylation signals and additionally specifies their origin to neuron, e.g., [[HOXA3]] or glia ([[ANK1]]). In a meta-analysis, we reveal two novel previously unrecognized methylation changes at the key AD risk genes [[APP]] and [[ADAM17]]. Our data highlight the complex interplay between disease, age and cell-type-specific methylation changes in AD risk genes thus offering new perspectives for the validation and interpretation of large EWAS results.
|mesh-terms=* ADAM17 Protein
* Aging
* Alzheimer Disease
* Amyloid beta-Protein Precursor
* Autopsy
* Cell Separation
* DNA Methylation
* Epigenesis, Genetic
* Epigenomics
* Genetic Predisposition to Disease
* Genome-Wide Association Study
* Humans
* Neuroglia
* Neurons
* Organ Specificity
* Transcriptome
|keywords=* Aging
* Alzheimer’s disease
* Brain
* Cell sorting
* DNA methylation
* EWAS
* Epigenetics
* Glia
* Neurodegeneration
* Neuron
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058387
}}
{{medline-entry
|title=Proteome profiling in the hippocampus, medial prefrontal cortex, and striatum of aging rat.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29981398
|abstract=Decrease in multiple functions occurs in the brain with aging, all of which can contribute to age-related cognitive and locomotor impairments. Brain atrophy specifically in hippocampus, medial prefrontal cortex (mPFC), and striatum, can contribute to this age-associated decline in function. Our recent metabolomics analysis showed age-related changes in these brain regions. To further understand the aging processes, analysis using a proteomics approach was carried out. This study was conducted to identify proteome profiles in the hippocampus, mPFC, and striatum of 14-, 18-, 23-, and 27-month-old rats. Proteomics analysis using ultrahigh performance liquid chromatography coupled with Q Exactive HF Orbitrap mass spectrometry identified 1074 proteins in the hippocampus, 871 proteins in the mPFC, and 241 proteins in the striatum. Of these proteins, 97 in the hippocampus, 25 in mPFC, and 5 in striatum were differentially expressed with age. The altered proteins were classified into three ontologies (cellular component, molecular function, and biological process) containing 44, 38, and 35 functional groups in the hippocampus, mPFC, and striatum, respectively. Most of these altered proteins participate in oxidative phosphorylation (e.g. cytochrome c oxidase and ATP synthase), glutathione metabolism (e.g. peroxiredoxins), or calcium signaling pathway (e.g. protein [[S100B]] and calmodulin). The most prominent changes were observed in the oldest animals. These results suggest that alterations in oxidative phosphorylation, glutathione metabolism, and calcium signaling pathway are involved in cognitive and locomotor impairments in aging.
|mesh-terms=* Aging
* Animals
* Atrophy
* Chromatography, Liquid
* Corpus Striatum
* Hippocampus
* Male
* Prefrontal Cortex
* Proteome
* Proteomics
* Rats
* Rats, Sprague-Dawley
|keywords=* Aging
* Brain
* Proteomics
|full-text-url=https://sci-hub.do/10.1016/j.exger.2018.07.002
}}
{{medline-entry
|title=Improving the clinical management of traumatic brain injury through the pharmacokinetic modeling of peripheral blood biomarkers.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27903281
|abstract=Blood biomarkers of neurovascular damage are used clinically to diagnose the presence severity or absence of neurological diseases, but data interpretation is confounded by a limited understanding of their dependence on variables other than the disease condition itself. These include half-life in blood, molecular weight, and marker-specific biophysical properties, as well as the effects of glomerular filtration, age, gender, and ethnicity. To study these factors, and to provide a method for markers' analyses, we developed a kinetic model that allows the integrated interpretation of these properties. The pharmacokinetic behaviors of [[S100B]] (monomer and homodimer), Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase L1 were modeled using relevant chemical and physical properties; modeling results were validated by comparison with data obtained from healthy subjects or individuals affected by neurological diseases. Brain imaging data were used to model passage of biomarkers across the blood-brain barrier. Our results show the following: (1) changes in biomarker serum levels due to age or disease progression are accounted for by differences in kidney filtration; (2) a significant change in the brain-to-blood volumetric ratio, which is characteristic of infant and adult development, contributes to variation in blood concentration of biomarkers; (3) the effects of extracranial contribution at steady-state are predicted in our model to be less important than suspected, while the contribution of blood-brain barrier disruption is confirmed as a significant factor in controlling markers' appearance in blood, where the biomarkers are typically detected; (4) the contribution of skin to the marker [[S100B]] blood levels depends on a direct correlation with pigmentation and not ethnicity; the contribution of extracranial sources for other markers requires further investigation. We developed a multi-compartment, pharmacokinetic model that integrates the biophysical properties of a given brain molecule and predicts its time-dependent concentration in blood, for populations of varying physical and anatomical characteristics. This model emphasizes the importance of the blood-brain barrier as a gatekeeper for markers' blood appearance and, ultimately, for rational clinical use of peripherally-detected brain protein.
|mesh-terms=* Aging
* Biomarkers
* Blood-Brain Barrier
* Brain Injuries, Traumatic
* Continental Population Groups
* Disease Management
* Disease Progression
* Female
* Glial Fibrillary Acidic Protein
* Humans
* Infant, Newborn
* Kidney
* Male
* Middle Aged
* Models, Cardiovascular
* Prospective Studies
* S100 Calcium Binding Protein beta Subunit
* Seasons
* Skin
* Skin Pigmentation
* Ubiquitin Thiolesterase
|keywords=* Glomerular filtration
* Physiologically-based pharmacokinetic model
* Precision medicine
* Serum markers
* Traumatic brain injury
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5402680
}}
{{medline-entry
|title=Sex-Specific Effects of Prenatal Stress on Memory and Markers of Neuronal Activity in Juvenile Rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27372837
|abstract=Stress during pregnancy can increase the incidence of emotional problems, learning and language difficulties in human infants and pre-adolescents. Most preclinical studies in rats that attempted to find experimental support for these observations were performed in adult male offspring, but the results are inconsistent. The aim of the current study was to examine the effect of prenatal stress on novel object recognition (NOR) and spatial learning and memory in the Morris water maze (MWM) of juvenile rats of both sexes. By the use of fluorescence immunohistochemistry and protein measurements by Western blot, we measured the expression of markers of neurogenesis (doublecortin, [[DCX]]) and neuronal activity that are important for synaptic plasticity and learning (c-fos, GluR1, nNOS). Since neuronal activity in the developing and adult brain can be regulated by astrocytes, we also measured the number of astrocytes and the expression of two astroglial proteins ([[GFAP]] and [[S100B]]) in the stress-responsive hippocampal dentate gyrus (DG). Experiments were performed on littermates of rats in which its effects on behavior were measured. We found for the first time that juvenile females performed better than males in the NOR and MWM tests. They also had higher densities of [[DCX]] and c-fos in the DG, together with the expression of nNOS and GluR1 in the subgranular zone (SGZ) of the DG. There were no sex differences in the expression of [[GFAP]] and [[S100B]] in astrocytes. Prenatal stress did not affect NOR in females, but improved it in males, together with an increase in [[DCX]]  and c-fos, the number of [[GFAP]]-expressing astrocytes and the intensity of [[GFAP]] and [[S100B]] immunofluorescence in the DG. Staining intensity of GluR1 and nNOS in the hilus and SGZ of the DG, and protein expression in the whole DG, was unchanged in prenatally stressed males. Thus, prenatal stress changed the behavior and expression of key proteins in the DG to resemble that in females. A reduction in plasma testosterone, which although not attaining statistical significance was associated with that in anogenital distance, may contribute to the effect of prenatal stress in males. In females, prenatal stress had no effect on c-fos, [[DCX]] or the number of astrocytes but reduced the staining intensity of GluR1 and nNOS. Protein expression of nNOS was also significantly lower than that in prenatally stressed males. The differential effects of prenatal stress on hippocampal neuronal and glial markers may help to explain the sex-dependent effect on spatial learning in prepubertal rats.
|mesh-terms=* Aging
* Animals
* Astrocytes
* Dentate Gyrus
* Female
* Hippocampus
* Memory
* Neurogenesis
* Neuronal Plasticity
* Neurons
* Pregnancy
* Prenatal Exposure Delayed Effects
* Rats, Wistar
* Sex Characteristics
* Stress, Physiological

|full-text-url=https://sci-hub.do/10.1159/000446981
}}
{{medline-entry
|title=Specific age-related molecular alterations in the cerebellum of Down syndrome mouse models.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27297494
|abstract=Down syndrome, or trisomy 21, has been modeled with various trisomic and transgenic mice to help understand the consequences of an altered gene dosage in brain development and function. Though Down syndrome has been associated with premature aging, little is known about the molecular and cellular alterations that target brain function. To help identify alterations at specific ages, we analyzed the cerebellum of Ts1Cje mice, trisomic for 77 HSA21 orthologs, at three ages-young (4 months), middle-age (12 months), and old (17 months)-compared to age-matched controls. Quantification of neuronal and glial markers (n=11) revealed increases in [[GFAP]], with an age effect, and [[S100B]], with age and genotype effects. The genotype effect on [[S100B]] with age was unexpected as Ts1Cje has only two copies of the S100b gene. Interestingly, the different increase in [[GFAP]] observed between Ts1Cje (trisomic segment includes Pcp4 gene) and controls was magnified in Tg[[PCP4]] mice (1 extra copy of the human [[PCP4]] gene) at the same age. [[S100B]] increase was not found in the Tg[[PCP4]] confirming a difference of regulation with aging for [[GFAP]] and [[S100B]] and excluding the calcium signaling regulator, Pcp4, as a potential candidate for increase of [[S100B]] in the Ts1Cje. To understand these differences, comparison of [[GFAP]] and [[S100B]] immunostainings at young and middle-age were performed. Immunohistochemical detection of differences in [[GFAP]] and [[S100B]] localization with aging implicate [[S100B]]  oligodendrocytes as a new phenotypic target in this specific aging process.
|mesh-terms=* Aging
* Animals
* Cerebellum
* Disease Models, Animal
* Down Syndrome
* Gene Dosage
* Gene Expression Regulation, Developmental
* Glial Fibrillary Acidic Protein
* Mice
* Mice, Transgenic
* Nerve Tissue Proteins
* Neuroglia
* Neurons
* Protein-Serine-Threonine Kinases
* Protein-Tyrosine Kinases
* S100 Calcium Binding Protein beta Subunit
* Trisomy
* Ubiquitination
|keywords=* Aging
* Cerebellum
* Down syndrome
* S100B
* Ts1Cje
|full-text-url=https://sci-hub.do/10.1016/j.brainres.2016.06.003
}}
{{medline-entry
|title=Age-dependent increase of blood-brain barrier permeability and neuron-binding autoantibodies in [[S100B]] knockout mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26907191
|abstract=[[S100B]] is a calcium-sensor protein that impacts multiple signal transduction pathways. It is widely considered to be an important biomarker for several neuronal diseases as well as blood-brain barrier (BBB) breakdown. In this report, we demonstrate a BBB deficiency in mice that lack [[S100B]] through detection of leaked Immunoglobulin G (IgG) in the brain parenchyma. IgG leaks and IgG-binding to selected neurons were observed in [[S100B]] knockout ([[S100B]]KO) mice at 6 months of age but not at 3 months. By 9 months, IgG leaks persisted and the density of IgG-bound neurons increased significantly. These results reveal a chronic increase in BBB permeability upon aging in [[S100B]]KO mice for the first time. Moreover, coincident with the increase in IgG-bound neurons, autoantibodies targeting brain proteins were detected in the serum via western blots. These events were concurrent with compromise of neurons, increase of activated microglia and lack of astrocytic activation as evidenced by decreased expression of microtubule-associated protein type 2 (MAP2), elevated number of [[CD68]] positive cells and unaltered expression of glial fibrillary acidic protein (GFAP) respectively. Results suggest a key role for [[S100B]] in maintaining BBB functional integrity and, further, propose the [[S100B]]KO mouse as a valuable model system to explore the link between chronic functional compromise of the BBB, generation of brain-reactive autoantibodies and neuronal dysfunctions. 
|mesh-terms=* Age Factors
* Animals
* Autoantibodies
* Blood-Brain Barrier
* Brain
* Immunoglobulin G
* Mice
* Mice, Knockout
* Microtubule-Associated Proteins
* Neurons
* Permeability
* S100 Calcium Binding Protein beta Subunit
|keywords=* Aging
* Autoantibodies
* Blood–brain barrier
* Neurodegenerative disease
* S100B
|full-text-url=https://sci-hub.do/10.1016/j.brainres.2016.02.026
}}
{{medline-entry
|title=Influence of Age on Cerebral Housekeeping Gene Expression for Normalization of Quantitative Polymerase Chain Reaction after Acute Brain Injury in Mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26102571
|abstract=To prevent methodological errors of quantitative PCR (qPCR) normalization with reference genes is obligatory. Although known to influence gene expression, impact of age on housekeeping gene expression has not been determined after acute brain lesions such as traumatic brain injury (TBI). Therefore, expression of eight common control genes was investigated at 15 min, 24 h, and 72 h after experimental TBI in 2- and 21-month-old C57Bl6 mice. Expression of β2-microglobulin (B2M), β-actin (ActB), and porphobilinogen deaminase (PBGD) increased after TBI in both ages. β2M demonstrated age-dependent differences and highest inter- and intragroup variations. Expression of cyclophilin A, glyceraldehyde-3-phosphate dehydrogenase ([[GAPDH]]), hypoxanthine ribosyltransferase (HPRT), [[S100B]], and 18SrRNA remained stable. Cyclophilin A and HPRT demonstrated strongest inter- and intragroup stability. The data indicate that the expression of most but not all control genes is stable during aging. The correct choice of housekeeping genes is of key importance to ensure adequate normalization of qPCR data. With respect to insult and age, normalization strategies should consider cyclophilin A as a single normalizer. Normalization with two reference genes is recommended with cyclophilin A and HPRT in young mice and in mixed age studies and with cyclophilin A and [[GAPDH]] in old mice. In addition, the present study suggests not to use β2-microglobulin, β-actin or PBGD as single control genes because of strong regulation after CCI in 2- and 21-month-old mice.
|mesh-terms=* Aging
* Animals
* Brain Chemistry
* Brain Injuries
* DNA, Complementary
* Gene Dosage
* Gene Expression Regulation
* Genes, Essential
* Interleukin-6
* Male
* Mice
* Mice, Inbred C57BL
* Polymerase Chain Reaction
* RNA
|keywords=* aging
* control genes
* housekeeping
* normalization
* quantitative real-time RT-PCR
* reference genes
* traumatic brain injury
|full-text-url=https://sci-hub.do/10.1089/neu.2014.3784
}}
{{medline-entry
|title=Amyloid-β immunotherapy reduces amyloid plaques and astroglial reaction in aged domestic dogs.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25531153
|abstract=Alzheimer's disease (AD) is characterized by the dynamic accumulation of extracellular amyloid deposits from the interplay between amyloid-β (Aβ) plaques, reactive astrocytes and activated microglia. Several immunotherapies against Aβ have been shown to reduce amyloid neuropathology. However, the role of the associated glia in the recovery process requires clarification. Previously, we described the safety and effectiveness in aged domestic canine with cognitive dysfunction syndrome of a new active vaccine candidate for the treatment of AD in humans. The aim of this article is to gain a better understanding of how immunotherapy modifies the amyloid burden and its effects on astroglial and microglial reactivity in immunized dogs. In order to achieve this, we compared and quantified amyloid plaques and astroglial and microglial reactions in the frontal cortex of unimmunized and immunized aged domestic dogs. We found amyloid plaques from immunized dogs to be smaller and more compact than those from unimmunized dogs. In these new plaques, the associated astrocytes were closer and less immunoreactive to the β subunit of S100 protein ([[S100B]]). We also found no modification in the microglial reaction associated with immunization. The anti-Aβ immunotherapy developed in our laboratory modifies the equilibrium between soluble and insoluble Aβ in aged dogs in close correlation with [[S100B]]-negative astrocytosis and microglial reaction.
|mesh-terms=* Aging
* Alzheimer Disease
* Amyloid beta-Peptides
* Animals
* Astrocytes
* Cognition Disorders
* Disease Models, Animal
* Dogs
* Female
* Frontal Lobe
* Immunization
* Immunoglobulin G
* Immunotherapy
* Male
* Plaque, Amyloid
* S100 Calcium Binding Protein beta Subunit

|full-text-url=https://sci-hub.do/10.1159/000368672
}}
{{medline-entry
|title=Postoperative impairment of cognitive function in old mice: a possible role for neuroinflammation mediated by [[HMGB1]], [[S100B]], and RAGE.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23899512
|abstract=Postoperative cognitive dysfunction, a common complication after surgery in elderly patients, is an increasing and largely underestimated problem without a defined etiology. Neuroinflammation plays an important role in the pathogenesis of postoperative cognitive dysfunction. The present study sought to investigate the role of neuroinflammation mediated by high-mobility group box 1 ([[HMGB1]]), [[S100B]], and the receptor for advanced glycation end product (RAGE) in cognitive dysfunction after partial hepatectomy in aged mice. Old C57BL/6 mice were randomly divided into three groups: normal control (n = 18), anesthetic (n = 66), and surgery (n = 66). The mice in the surgery or anesthetic group received isoflurane anesthesia for either partial hepatectomy or no surgery, respectively. Cognitive function was subsequently assessed using a Y-maze. [[HMGB1]], [[S100B]], RAGE, interleukin-1β, and nuclear factor-kappaB p65 levels were measured at 12 h and 1, 3, and 7 d after surgery. Immunofluorescence double labeling was performed to study the colocalization between RAGE and its ligands, [[HMGB1]] and [[S100B]]. The mice's learning and memory abilities were significantly impaired at 1 and 3 d and 2 and 4 d after surgery, respectively. The expression of [[HMGB1]], [[S100B]], RAGE, and nuclear factor-kappaB p65 had increased significantly at 12 h and 1 and 3 d after surgery. The interleukin-1β level was significantly increased at 1 and 3 d after surgery. The interaction of [[HMGB1]] or [[S100B]] with RAGE was confirmed at 1 d after surgery. These data suggest that [[HMGB1]], [[S100B]], and RAGE signaling modulate the hippocampal inflammatory response and might play key roles in surgery-induced cognitive decline.
|mesh-terms=* Aging
* Animals
* Astrocytes
* Cognition Disorders
* HMGB1 Protein
* Hepatectomy
* Interleukin-1beta
* Male
* Maze Learning
* Memory
* Mice
* Mice, Inbred C57BL
* Neuritis
* Neuroimmunomodulation
* Postoperative Complications
* Random Allocation
* Receptor for Advanced Glycation End Products
* Receptors, Immunologic
* S100 Calcium Binding Protein beta Subunit
|keywords=* High mobility group box-1
* Neuroinflammation
* Postoperative cognitive dysfunction
* Receptor for advanced glycation end products
* S100B
|full-text-url=https://sci-hub.do/10.1016/j.jss.2013.06.043
}}
{{medline-entry
|title=Serum [[S100B]] represents a new biomarker for mood disorders.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23701298
|abstract=Recently, mood disorders have been discussed to be characterized by glial pathology. The protein [[S100B]], a growth and differentiation factor, is located in, and may actively be released by astro- and oligodendrocytes. This protein is easily assessed in human serum and provides a useful parameter for glial activation or injury. Here, we review studies investigating the glial marker [[S100B]] in serum of patients with mood disorders. Studies consistently show that [[S100B]] is elevated in mood disorders; more strongly in major depressive than bipolar disorder. Consistent with the glial hypothesis of mood disorders, serum [[S100B]] levels interact with age with higher levels in elderly depressed subjects. Successful antidepressive treatment has been associated with serum [[S100B]] reduction in major depression, whereas there is no evidence of treatment effects in mania. In contrast to the glial marker [[S100B]], the neuronal marker protein neuron-specific enolase is unaltered in mood disorders. Recently, serum [[S100B]] has been linked to specific imaging parameters in the human white matter suggesting a role for [[S100B]] as an oligodendrocytic marker protein. In sum, serum [[S100B]] can be regarded as a promising in vivo biomarker for mood disorders deepening the understanding of the pathogenesis and plasticity-changes in these disorders. Future longitudinal studies combining serum [[S100B]] with other cell-specific serum parameters and multimodal imaging are warranted to further explore this serum protein in the development, monitoring and treatment of mood disorders. 
|mesh-terms=* Aged
* Aging
* Animals
* Antidepressive Agents
* Biomarkers
* Humans
* Mood Disorders
* Neuroglia
* Neuronal Plasticity
* Phosphopyruvate Hydratase
* S100 Calcium Binding Protein beta Subunit

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821390
}}
{{medline-entry
|title=Intraperitoneal treatment with [[S100B]] enhances hippocampal neurogenesis in juvenile mice and after experimental brain injury.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23649988
|abstract=Neurogenesis is documented in adult mammals including humans, is promoted by neurotrophic factors, and constitutes an innate repair mechanism following brain injury. The glial neurotrophic protein [[S100B]] is released following various types of brain injuries, enhances hippocampal neurogenesis and improves cognitive function following brain injury in rats when applied intrathecally. The present study was designed to elucidate whether the beneficial effect of [[S100B]] on injury-induced neurogenesis can be confirmed in mice when applied intraperitoneally (i.p.), and whether this effect is dose-dependent. Male juvenile mice were subjected to a unilateral parietal cryolesion or sham injury, and treated with [[S100B]] at 20nM, 200nM or vehicle i.p. once daily. Hippocampal progenitor cell proliferation was quantified following labelling with bromo-deoxyuridine (BrdU, 50 mg/KG i.p.) in the germinative area of the dentate gyrus, the subgranular zone (SGZ), on day 4 as well as on cell survival and migration to the granular cell layer (GCL) on day 28. Progenitor cell differentiation was assessed following colabelling with the glial marker [[GFAP]] and the neuronal marker NeuN. [[S100B]] enhanced significantly the early progenitor cell proliferation in the SGZ as well as cell survival and migration to the GCL, and promoted neuronal differentiation. While these effects were predominately dose-dependent, 200nM [[S100B]] failed to enhance the proliferation in the SGZ on day 4 post-injury. We conclude that [[S100B]] participates in hippocampal neurogenesis after injury at lower nanomolar concentrations. Therefore [[S100B]] may serve as a potential adjunct treatment to promote neuroregeneration following brain damage.
|mesh-terms=* Aging
* Animals
* Brain Injuries
* Cell Differentiation
* Cell Proliferation
* Dentate Gyrus
* Disease Models, Animal
* Hippocampus
* Male
* Mice
* Mice, Inbred C57BL
* Neurogenesis
* Neuroglia
* Neurons
* S100 Calcium Binding Protein beta Subunit
* Stem Cells

|full-text-url=https://sci-hub.do/10.1007/s00701-013-1720-2
}}