Effects and Mechanisms of Synaptotagmin-7 in the Hippocampus on Cognitive Impairment in Aging Mice.
Aging
/ metabolism
Animals
CA1 Region, Hippocampal
/ physiopathology
Cognition Disorders
/ physiopathology
Conditioning, Classical
Dependovirus
/ genetics
Electroshock
Fear
/ physiology
Galactose
/ toxicity
Gene Expression Regulation
Genes, Reporter
Genes, p16
Genes, p53
Genetic Vectors
/ administration & dosage
Long-Term Potentiation
Male
Memory Disorders
/ chemically induced
Mice
Mice, Inbred C57BL
Morris Water Maze Test
Nerve Tissue Proteins
/ physiology
Random Allocation
Recognition, Psychology
Recombinant Proteins
/ metabolism
Spatial Learning
/ drug effects
Specific Pathogen-Free Organisms
Synaptotagmins
/ genetics
Synaptotagmin-7; Overexpression; Cognitive impairment; Hippocampus; Long-term potentiation
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Nov 2021
Nov 2021
Historique:
received:
04
02
2021
accepted:
08
08
2021
pubmed:
18
8
2021
medline:
25
3
2022
entrez:
17
8
2021
Statut:
ppublish
Résumé
Aging is an irreversible biological process that involves oxidative stress, neuroinflammation, and apoptosis, and eventually leads to cognitive dysfunction. However, the underlying mechanisms are not fully understood. In this study, we investigated the role and potential mechanisms of Synaptotagmin-7, a calcium membrane transporter in cognitive impairment in aging mice. Our results indicated that Synaptotagmin-7 expression significantly decreased in the hippocampus of D-galactose-induced or naturally aging mice when compared with healthy controls, as detected by western blot and quantitative reverse transcriptase-polymerase chain reaction analysis. Synaptotagmin-7 overexpression in the dorsal CA1 of the hippocampus reversed long-term potentiation and improved hippocampus-dependent spatial learning in D-galactose-induced aging mice. Synaptotagmin-7 overexpression also led to fully preserved learning and memory in 6-month-old mice. Mechanistically, we demonstrated that Synaptotagmin-7 improved learning and memory by elevating the level of fEPSP and downregulating the expression of aging-related genes such as p53 and p16. The results of our study provide new insights into the role of Synaptotagmin-7 in improving neuronal function and overcoming memory impairment caused by aging, suggesting that Synaptotagmin-7 overexpression may be an innovative therapeutic strategy for treating cognitive impairment.
Identifiants
pubmed: 34403042
doi: 10.1007/s12035-021-02528-1
pii: 10.1007/s12035-021-02528-1
doi:
Substances chimiques
Nerve Tissue Proteins
0
Recombinant Proteins
0
Syt7 protein, mouse
0
Synaptotagmins
134193-27-4
Galactose
X2RN3Q8DNE
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5756-5771Subventions
Organisme : National Natural Science Foundation of China
ID : 81471490
Organisme : National Natural Science Foundation of China
ID : 81671066
Organisme : National Natural Science Foundation of China
ID : 81974162
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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