Редактирование: CA1 (раздел)

==Publications==

{{medline-entry
|title=A novel structure associated with aging is augmented in the [[DPP6]]-KO mouse brain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33225987
|abstract=In addition to its role as an auxiliary subunit of A-type voltage-gated K  channels, we have previously reported that the single transmembrane protein Dipeptidyl Peptidase Like 6 ([[DPP6]]) impacts neuronal and synaptic development. [[DPP6]]-KO mice are impaired in hippocampal-dependent learning and memory and exhibit smaller brain size. Using immunofluorescence and electron microscopy, we report here a novel structure in hippocampal area [[CA1]] that was significantly more prevalent in aging [[DPP6]]-KO mice compared to WT mice of the same age and that these structures were observed earlier in development in [[DPP6]]-KO mice. These novel structures appeared as clusters of large puncta that colocalized NeuN, synaptophysin, and chromogranin A. They also partially labeled for [[MAP2]], and with synapsin-1 and VGluT1 labeling on their periphery. Electron microscopy revealed that these structures are abnormal, enlarged presynaptic swellings filled with mainly fibrous material with occasional peripheral, presynaptic active zones forming synapses. Immunofluorescence imaging then showed that a number of markers for aging and especially Alzheimer's disease were found as higher levels in these novel structures in aging [[DPP6]]-KO mice compared to WT. Together these results indicate that aging [[DPP6]]-KO mice have increased numbers of novel, abnormal presynaptic structures associated with several markers of Alzheimer's disease.

|keywords=* Aging dementia
* Alzheimer’s disease
* DPP6
* Presynaptic terminals
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682109
}}
{{medline-entry
|title=Alterations in Intrinsic and Synaptic Properties of Hippocampal [[CA1]] [[VIP]] Interneurons During Aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33173468
|abstract=Learning and memory deficits are hallmarks of the aging brain, with cortical neuronal circuits representing the main target in cognitive deterioration. While GABAergic inhibitory and disinhibitory circuits are critical in supporting cognitive processes, their roles in age-related cognitive decline remain largely unknown. Here, we examined the morphological and physiological properties of the hippocampal [[CA1]] vasoactive intestinal peptide/calretinin-expressing ([[VIP]] /CR ) type 3 interneuron-specific (I-S3) cells across mouse lifespan. Our data showed that while the number and morphological features of I-S3 cells remained unchanged, their firing and synaptic properties were significantly altered in old animals. In particular, the action potential duration and the level of steady-state depolarization were significantly increased in old animals in parallel with a significant decrease in the maximal firing frequency. Reducing the fast-delayed rectifier potassium or transient sodium conductances in I-S3 cell computational models could reproduce the age-related changes in I-S3 cell firing properties. However, experimental data revealed no difference in the activation properties of the Kv3.1 and A-type potassium currents, indicating that transient sodium together with other ion conductances may be responsible for the observed phenomena. Furthermore, I-S3 cells in aged mice received a stronger inhibitory drive due to concomitant increase in the amplitude and frequency of spontaneous inhibitory currents. These age-associated changes in the I-S3 cell properties occurred in parallel with an increased inhibition of their target interneurons and were associated with spatial memory deficits and increased anxiety. Taken together, these data indicate that [[VIP]] /CR  interneurons responsible for local circuit disinhibition survive during aging but exhibit significantly altered physiological properties, which may result in the increased inhibition of hippocampal interneurons and distorted mnemonic functions.

|keywords=* VIP
* action potential
* aging
* calretinin
* circuit disinhibition
* hippocampus
* synapse
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591401
}}
{{medline-entry
|title=Abolishing [[UCHL1]]'s hydrolase activity exacerbates TBI-induced axonal injury and neuronal death in mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33159930
|abstract=Ubiquitin (Ub) C-terminal hydrolase L1 ([[UCHL1]]) is a multifunctional protein that is expressed in neurons throughout brain at high levels. [[UCHL1]] deletion is associated with axonal degeneration, progressive sensory motor ataxia, and premature death in mice. [[UCHL1]] has been hypothesized to play a role in the pathogenesis of neurodegenerative diseases and recovery after neuronal injury. [[UCHL1]] hydrolyzes Ub from polyubiquitinated (poly-Ub) proteins, but also may ligate Ub to select neuronal proteins, and interact with cytoskeletal proteins. These and other mechanisms have been hypothesized to underlie [[UCHL1]]'s role in neurodegeneration and response to brain injury. A [[UCHL1]] knockin mouse containing a C90A mutation (C90A) devoid of hydrolase activity was constructed. The C90A mouse did not develop the sensory and motor deficits, degeneration of the gracile nucleus and tract, or premature death as seen in [[UCHL1]] deficient mice. C90A and wild type (WT) mice were subjected to the controlled cortical impact (CCI) model of traumatic brain injury (TBI), and cell death, axonal injury and behavioral outcome were assessed. C90A mice exhibited decreased spared tissue volume, greater loss of [[CA1]] hippocampal neurons and greater axonal injury as detected using anti-amyloid precursor protein (APP) antibody and anti- non-phosphorylated neurofilament H (SMI-32) antibody immunohistochemistry after CCI compared to WT controls. Poly-Ub proteins and Beclin-1 were elevated after CCI in C90A mice compared to WT controls. Vestibular motor deficits assessed using the beam balance test resolved by day 5 after CCI in WT mice but not in C90A mice. These results suggest that the hydrolase activity of [[UCHL1]] does not account for the progressive neurodegeneration and premature death seen in mice that do not express full length [[UCHL1]]. The hydrolase activity of [[UCHL1]] contributes to the function of the ubiquitin proteasome pathway (UPP), ameliorates activation of autophagy, and improves motor recovery after CCI. Thus, [[UCHL1]] hydrolase activity plays an important role in acute injury response after TBI.

|keywords=* Aging
* Axonal injury
* Neurodegeneration
* Traumatic brain injury
* Ubiquitin carboxy terminal hydrolase L1
* Ubiquitin proteasome pathway
|full-text-url=https://sci-hub.do/10.1016/j.expneurol.2020.113524
}}
{{medline-entry
|title=The relation between tau pathology and granulovacuolar degeneration of neurons.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33069844
|abstract=Neurofibrillary tangles arising from aggregated microtubule-associated protein tau occur in aged brains and are hallmarks of neurodegenerative diseases. A subset of neurons containing aggregated tau displays granulovacuolar degeneration (GVD) that is characterized by membrane-bound cytoplasmic vacuoles, each containing an electron-dense granule (GVB). Tau pathology induces GVBs in experimental models, but GVD does not generally follow tau pathology in the human brain. The entorhinal cortex, DRN, and LC are among the regions that display pathological changes of tau earliest, whereas neurons with GVBs occur first in the hippocampus and have been found in oral raphe nuclei only at the most advanced GVD stage. To date, there is no detailed report about neurons with GVD in aminergic nuclei. We studied the relation between tau pathology and GVD in field [[CA1]] of the hippocampus, entorhinal cortex, dorsal (DRN) and median (MRN) raphe nucleus, and locus coeruleus from elderly subjects with Braak