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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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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 |
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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 |
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