Cargando…

AAV Delivery of shRNA Against TRPC6 in Mouse Hippocampus Impairs Cognitive Function

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 h...

Descripción completa

Detalles Bibliográficos
Autores principales: Xie, Ruxin, Wang, Zhongke, Liu, Tianyao, Xiao, Rui, Lv, Keyi, Wu, Chuan, Luo, Yi, Cai, Yun, Fan, Xiaotang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313999/
https://www.ncbi.nlm.nih.gov/pubmed/34327201
http://dx.doi.org/10.3389/fcell.2021.688655
_version_ 1783729459690471424
author Xie, Ruxin
Wang, Zhongke
Liu, Tianyao
Xiao, Rui
Lv, Keyi
Wu, Chuan
Luo, Yi
Cai, Yun
Fan, Xiaotang
author_facet Xie, Ruxin
Wang, Zhongke
Liu, Tianyao
Xiao, Rui
Lv, Keyi
Wu, Chuan
Luo, Yi
Cai, Yun
Fan, Xiaotang
author_sort Xie, Ruxin
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8313999
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-83139992021-07-28 AAV Delivery of shRNA Against TRPC6 in Mouse Hippocampus Impairs Cognitive Function Xie, Ruxin Wang, Zhongke Liu, Tianyao Xiao, Rui Lv, Keyi Wu, Chuan Luo, Yi Cai, Yun Fan, Xiaotang Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2021-07-13 /pmc/articles/PMC8313999/ /pubmed/34327201 http://dx.doi.org/10.3389/fcell.2021.688655 Text en Copyright © 2021 Xie, Wang, Liu, Xiao, Lv, Wu, Luo, Cai and Fan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Xie, Ruxin
Wang, Zhongke
Liu, Tianyao
Xiao, Rui
Lv, Keyi
Wu, Chuan
Luo, Yi
Cai, Yun
Fan, Xiaotang
AAV Delivery of shRNA Against TRPC6 in Mouse Hippocampus Impairs Cognitive Function
title AAV Delivery of shRNA Against TRPC6 in Mouse Hippocampus Impairs Cognitive Function
title_full AAV Delivery of shRNA Against TRPC6 in Mouse Hippocampus Impairs Cognitive Function
title_fullStr AAV Delivery of shRNA Against TRPC6 in Mouse Hippocampus Impairs Cognitive Function
title_full_unstemmed AAV Delivery of shRNA Against TRPC6 in Mouse Hippocampus Impairs Cognitive Function
title_short AAV Delivery of shRNA Against TRPC6 in Mouse Hippocampus Impairs Cognitive Function
title_sort aav delivery of shrna against trpc6 in mouse hippocampus impairs cognitive function
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313999/
https://www.ncbi.nlm.nih.gov/pubmed/34327201
http://dx.doi.org/10.3389/fcell.2021.688655
work_keys_str_mv AT xieruxin aavdeliveryofshrnaagainsttrpc6inmousehippocampusimpairscognitivefunction
AT wangzhongke aavdeliveryofshrnaagainsttrpc6inmousehippocampusimpairscognitivefunction
AT liutianyao aavdeliveryofshrnaagainsttrpc6inmousehippocampusimpairscognitivefunction
AT xiaorui aavdeliveryofshrnaagainsttrpc6inmousehippocampusimpairscognitivefunction
AT lvkeyi aavdeliveryofshrnaagainsttrpc6inmousehippocampusimpairscognitivefunction
AT wuchuan aavdeliveryofshrnaagainsttrpc6inmousehippocampusimpairscognitivefunction
AT luoyi aavdeliveryofshrnaagainsttrpc6inmousehippocampusimpairscognitivefunction
AT caiyun aavdeliveryofshrnaagainsttrpc6inmousehippocampusimpairscognitivefunction
AT fanxiaotang aavdeliveryofshrnaagainsttrpc6inmousehippocampusimpairscognitivefunction