AAV Delivery of shRNA Against TRPC6 in Mouse Hippocampus Impairs Cognitive Function.
TRPC6
cognitive process
hippocampus
shRNA
synapse
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2021
2021
Historique:
received:
31
03
2021
accepted:
22
06
2021
entrez:
30
7
2021
pubmed:
31
7
2021
medline:
31
7
2021
Statut:
epublish
Résumé
Transient Receptor Potential Canonical 6 (TRPC6) has been suggested to be involved in synapse function and contribute to hippocampal-dependent cognitive processes. Gene silencing of TRPC6 was performed by injecting adeno-associated virus (AAV) expressing TRPC6-specific shRNA (shRNA-TRPC6) into the hippocampal dentate gyrus (DG). Spatial learning, working memory and social recognition memory were impaired in the shRNA-TRPC6 treated mice compared to control mice after 4 weeks. In addition, gene ontology (GO) analysis of RNA-sequencing revealed that viral intervention of TRPC6 expression in DG resulted in the enrichment of the process of synaptic transmission and cellular compartment of synaptic structure. KEGG analysis showed PI3K-Akt signaling pathway were significantly down-regulated. Furthermore, the shRNA-TRPC6 treatment reduced dendritic spines of DG granule neurons, in terms of spine loss, the thin and mushroom types predominated. Accompanying the spine loss, the levels of PSD95, pAkt and CREB in the hippocampus were decreased in the shRNA-TRPC6 treated animals. Taken together, our results suggest that knocking down TRPC6 in the DG have a disadvantageous effect on cognitive processes.
Identifiants
pubmed: 34327201
doi: 10.3389/fcell.2021.688655
pmc: PMC8313999
doi:
Types de publication
Journal Article
Langues
eng
Pagination
688655Informations de copyright
Copyright © 2021 Xie, Wang, Liu, Xiao, Lv, Wu, Luo, Cai and Fan.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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