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Carbonic anhydrase 2 (EC 4.2.1.1) (Carbonate dehydratase II) (Carbonic anhydrase C) (CAC) (Carbonic anhydrase II) (CA-II)

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Maintaining Aging Hippocampal Function with Safe and Feasible Shaking Exercise in SAMP10 Mice.

The disabling effects of dementia, an incurable disease with little effect on mortality, affect society far more than many other conditions. The aim of this study was to stop or delay the onset of dementia using low-cost methods such as physical exercise. Senescence-accelerated model-prone (SAMP) 10 mice were made to perform a user-friendly shaking exercise for 25 weeks. The motor function and hippocampal functions (learning, spatial cognition) of the mice were evaluated using behavioral experiments. The degree of hippocampal aging was evaluated based on brain morphology. The association between behavioral performance of the mice and the degree of hippocampal aging was then evaluated. The behavioral test results showed that the shaking group had higher motor coordination (p < 0.01) and motor learning (p < 0.05). Significantly higher performances in the learning ability were observed in the shaking group at a middle-period experiment (p < 0.05); the spatial cognitive functions also improved (p < 0.05). The shaking group showed delayed ageing of cells in the dentate gyrus (DG; area: p < 0.01) and cornu Ammonis (CA; area: p < 0.01) regions of the hippocampus. The shaking exercise enhances the activity of mice and reduces age-associated decreases in learning and spatial cognitive functions. Regarding hippocampal morphology, shaking exercise can prevent non-functional protein accumulation, cell atrophy, and cell loss. Specifically, shaking exercise protects cell growth and regeneration in the DG area and enhances the learning function of the hippocampus. Furthermore, shaking exercise maintained the spatial cognitive function of cells in the CA3 and CA1 regions, and prevented the chronic loss of CA2 transmission that decreased the spatial memory decline in mice.


Keywords

  • Aging
  • Behavior analysis
  • Hippocampus
  • Shaking exercise
  • Spatial cognition


One-year Follow-up Study of Hippocampal Subfield Atrophy in Alzheimer's Disease and Normal Aging.

In this study, we investigated the effect of hippocampal subfield atrophy on the development of Alzheimer's disease (AD) by analyzing baseline magnetic resonance images (MRI) and images collected over a one-year follow-up period. Previous studies have suggested that morphological changes to the hippocampus are involved in both normal ageing and the development of AD. The volume of the hippocampus is an authentic imaging biomarker for AD. However, the diverse relationship of anatomical and complex functional connectivity between different subfields implies that neurodegenerative disease could lead to differences between the atrophy rates of subfields. Therefore, morphometric measurements at subfield-level could provide stronger biomarkers. Hippocampal subfield atrophies are measured using MRI scans, taken at multiple time points, and shape-based normalization to a Montreal neurological institute (MNI) ICBM 152 nonlinear atlas. Ninety subjects were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI), and divided equally into Healthy Controls (HC), AD, and mild cognitive impairment (MCI) groups. These subjects underwent serial MRI studies at three time-points: baseline, 6 months and 12 months. We analyzed the subfield-level hippocampal morphometric effects of normal ageing and AD based on radial distance mapping and volume measurements. We identified a general trend and observed the largest hippocampal subfield atrophies in the AD group. Atrophy of the bilateral CA1, CA2- CA4 and subiculum subfields was higher in the case of AD than in MCI and HC. We observed the highest rate of reduction in the total volume of the hippocampus, especially in the CA1 and subiculum regions, in the case of MCI. Our findings show that hippocampal subfield atrophy varies among the three study groups.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Alzheimer Disease
  • Atrophy
  • Case-Control Studies
  • Cognitive Dysfunction
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Hippocampus
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neuroimaging

Keywords

  • Alzheimer's disease
  • biomarker
  • hippocampal
  • mild cognitive impairment
  • neurodegenerative diseases
  • normal aging
  • radial distance
  • subfield atrophy


Maturation of PNN and ErbB4 Signaling in Area CA2 during Adolescence Underlies the Emergence of PV Interneuron Plasticity and Social Memory.

Adolescence is a vulnerable period characterized by major cognitive changes. The mechanisms underlying the emergence of new cognitive functions are poorly understood. We find that a long-term depression of inhibitory transmission (iLTD) from parvalbumin-expressing (PV ) interneurons in the hippocampal area Cornu Ammonis 2 (CA2) is absent in young mice but emerges at the end of adolescence. We demonstrate that the maturation of both the perineuronal net (PNN) and signaling through ErbB4 is required for this plasticity. Furthermore, we demonstrate that social recognition memory displays the same age dependence as iLTD and is impaired by targeted degradation of the PNN or iLTD blockade in area CA2. Our data reveal an unusual developmental rule for plasticity at the PV interneuron transmission in area CA2 and indicate that this plasticity is involved in the emergence of higher cognitive function, such as social memory formation, in late adolescence.

MeSH Terms

  • Aging
  • Animals
  • Animals, Newborn
  • CA2 Region, Hippocampal
  • Interneurons
  • Long-Term Synaptic Depression
  • Male
  • Memory
  • Mice
  • Mice, Inbred C57BL
  • Neural Inhibition
  • Neuregulin-1
  • Neuronal Plasticity
  • Parvalbumins
  • Receptor, ErbB-4
  • Receptors, Opioid, delta
  • Signal Transduction
  • Social Behavior
  • Synapses
  • gamma-Aminobutyric Acid

Keywords

  • ErbB4
  • adolescence
  • area CA2
  • delta opioid receptors
  • hippocampus
  • long-term depression
  • neuregulin 1
  • parvalbumin interneuron
  • perineuronal net
  • social memory


Early disruption of parvalbumin expression and perineuronal nets in the hippocampus of the Tg2576 mouse model of Alzheimer's disease can be rescued by enriched environment.

Recent findings show that parvalbumin (PV) interneuron function is impaired in Alzheimer's disease (AD), and that this impairment in PV function can be linked to network dysfunction and memory deficits. PV cells are often associated with a specific extracellular matrix, the perineuronal net (PNN). PNNs are believed to protect PV cell integrity, and whether the amyloidopathy affects PNNs remains unclear. Here, we evaluated the number of PV cells with and without PNNs in the hippocampus of the Tg2576 mouse model of AD at different stages of the disease. We show a deficit of PV and/or PV /PNN cells in the areas CA1, CA2, and CA3 in Tg2576 as young as 3 months of age. Importantly, transient exposure to an enriched environment, which has proven long-lasting beneficial effects on memory in AD subjects, rescues the PV/PNN cell number deficits. We conclude that cognitive improvements induced by enriched environment in AD mouse models could be supported by a remodeling of hippocampal PV cell network and their PNNs.

MeSH Terms

  • Age Factors
  • Aging
  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Animals
  • Disease Models, Animal
  • Environment
  • Extracellular Matrix
  • Female
  • Hippocampus
  • Interneurons
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Parvalbumins

Keywords

  • Alzheimer's disease
  • Enriched housing
  • Hippocampus
  • Parvalbumin-expressing interneuron
  • Perineuronal net


Protracted hippocampal development is associated with age-related improvements in memory during early childhood.

The hippocampus is a structure that is critical for memory. Previous studies have shown that age-related differences in specialization along the longitudinal axis of this structure (i.e., subregions) and within its internal circuitry (i.e., subfields) relate to age-related improvements in memory in school-age children and adults. However, the influence of age on hippocampal development and its relations with memory ability earlier in life remains under-investigated. This study examined effects of age and sex on hippocampal subregion (i.e., head, body, tail) and subfield (i.e., subiculum, CA1, CA2-4/DG) volumes, and their relations with memory, using a large sample of 4- to 8-year-old children. Results examining hippocampal subregions suggest influences of both age and sex on the hippocampal head during early childhood. Results examining subfields within hippocampal head suggest these age effects may arise from CA1, whereas sex differences may arise from subiculum and CA2-4/DG. Memory ability was not associated with hippocampal subregion volume but was associated with subfield volume. Specifically, within the hippocampal head, relations between memory and CA1 were moderated by age; in younger children bigger was better, whereas in older children smaller was superior. Within the hippocampal body, smaller CA1 and larger CA2-4/DG contributed to better memory performance across all ages. Together, these results shed light on hippocampal development during early childhood and support claims that the prolonged developmental trajectory of the hippocampus contributes to memory development early in life.

MeSH Terms

  • Aging
  • Brain Mapping
  • Child
  • Child Development
  • Child, Preschool
  • Female
  • Hippocampus
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory
  • Sex Characteristics

Keywords

  • Development
  • Early childhood
  • Hippocampus
  • Memory


Neurodevelopment and behavior in neonatal OXYS rats with genetically determined accelerated senescence.

Study of the developmental characteristics and mechanisms of senescence is an important field in brain aging research. The OXYS strain was selected from Wistar rats in Novosibirsk, and it serves as a rat model of accelerated aging. Previously, neurodegenerative processes and aberrant behavior were reported in experiments with adult OXYS rats. In our study, neurodevelopmental reflexes, neuronal density in the prefrontal cortex and hippocampus, and global DNA methylation in the hippocampus are compared between OXYS and WAG (Wistar Albino Glaxo) neonatal pups. The development of the righting, forelimb grasp, and cliff avoidance reflexes is delayed, and body weight gain was deferred in neonatal OXYS pups. Neuronal density in the hippocampus does not differ between one-day-old OXYS and WAG pups. On the sixth day, the neuronal density in OXYS pups is reduced in the CA2 hippocampal zone, augmented in CA3 and DG, and unchanged in CA1. Six-day-old OXYS pups have fewer and smaller pyramidal neurons in the prefrontal cortex as compared to WAG controls. Global DNA methylation levels in the hippocampus of OXYS newborns are significantly lower than in the WAG newborn pups. At the age of six days, the global DNA methylation level decreases in WAG pups, but does not change in OXYS pups. Thus, neonatal OXYS rats show delayed neurodevelopment accompanied by changes in the global DNA methylation pattern in the hippocampus and in neuronal density in the hippocampus and the prefrontal cortex. These changes may be related to accelerated senescence in adult OXYS rats.

MeSH Terms

  • Aging
  • Animals
  • Animals, Newborn
  • Behavior, Animal
  • Cell Count
  • DNA Methylation
  • Female
  • Hippocampus
  • Male
  • Neurons
  • Prefrontal Cortex
  • Rats, Transgenic
  • Rats, Wistar
  • Reflex

Keywords

  • Global DNA methylation
  • Hippocampus
  • Neurodevelopmental reflexes
  • Neuronal density
  • OXYS rats
  • Prefrontal cortex


Effect of Chronic Administration of Resveratrol on Cognitive Performance during Aging Process in Rats.

The increase in the elderly population has generated concern to meet health demands. The research efforts to elucidate the mechanisms of damage associated with aging have also been significantly increased, especially in order to avoid the reduction of the cognitive abilities in geriatric patients, resulting from the damage generated mainly at the level of the hippocampus during old age. At present, many studies describe resveratrol as an antiaging component. There are reports that it can activate the Sirt1 gene related to antiaging, emulating the effects obtained by caloric restriction in rodents. The aim of the study was to evaluate the effect of chronic administration of resveratrol (10 mg/kg) on cognitive performance in behavioral tests after 8 months of treatment and on the preservation of cerebral integrity in the cytoarchitecture of regions CA1 and CA2. Results showed that the cytoarchitecture of the CA1 and CA2 regions in the hippocampus retained their integrity over time in rats treated with resveratrol, and the behavioral test performed revealed that chronic resveratrol administration for 8 months showed improvements in cognitive performance. The results indicate that resveratrol may exhibit therapeutic potential for age-related conditions.

MeSH Terms

  • Aging
  • Animals
  • Cognition
  • Drug Administration Routes
  • Male
  • Rats
  • Rats, Wistar
  • Resveratrol
  • Stilbenes

{{medline-entry |title=Time of day but not aging regulates 5-HT receptor binding sites in the hamster hippocampus. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29107707 |abstract=Activation of 5-HT receptors influences memory as well as circadian rhythms and other processes. This study investigated the regulation of the 5-HT receptors in the hippocampus, a likely substrate for the effects of 5-HT receptor compounds on memory. Because endogenous serotonin release is higher during the active phase, and chronic treatment with a serotonin-selective reuptake inhibitor down-regulates 5-HT receptors, we hypothesized that 5-HT receptors exhibit 24-h variations. We also hypothesized that aging decreases 5-HT receptors in the hippocampus, as it does in the dorsal raphe nucleus, a brain site for serotonergic resetting of circadian rhythms. Male hamsters (young, 3-5 mos; old, 17-21 mos) exposed to a light:dark cycle were euthanized at 4 times of day (zeitgeber times [ZT]1, 6, 13,