Overexpression of SIRT6 in the hippocampal CA1 impairs the formation of long-term contextual fear memory

Histone modifications have been implicated in learning and memory. Our previous transcriptome data showed that expression of sirtuins 6 (SIRT6), a member of Histone deacetylases (HDACs) family in the hippocampal cornu ammonis 1 (CA1) was decreased after contextual fear conditioning. However, the rol...

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Main Authors:	Yin, Xi, Gao, Yuan, Shi, Hai-Shui, Song, Li, Wang, Jie-Chao, Shao, Juan, Geng, Xu-Hong, Xue, Gai, Li, Jian-Li, Hou, Yan-Ning
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702175/

id	pubmed-4702175
recordtype	oai_dc
spelling	pubmed-47021752016-01-14 Overexpression of SIRT6 in the hippocampal CA1 impairs the formation of long-term contextual fear memory Yin, Xi Gao, Yuan Shi, Hai-Shui Song, Li Wang, Jie-Chao Shao, Juan Geng, Xu-Hong Xue, Gai Li, Jian-Li Hou, Yan-Ning Article Histone modifications have been implicated in learning and memory. Our previous transcriptome data showed that expression of sirtuins 6 (SIRT6), a member of Histone deacetylases (HDACs) family in the hippocampal cornu ammonis 1 (CA1) was decreased after contextual fear conditioning. However, the role of SIRT6 in the formation of memory is still elusive. In the present study, we found that contextual fear conditioning inhibited translational expression of SIRT6 in the CA1. Microinfusion of lentiviral vector-expressing SIRT6 into theCA1 region selectively enhanced the expression of SIRT6 and impaired the formation of long-term contextual fear memory without affecting short-term fear memory. The overexpression of SIRT6 in the CA1 had no effect on anxiety-like behaviors or locomotor activity. Also, we also found that SIRT6 overexpression significantly inhibited the expression of insulin-like factor 2 (IGF2) and amounts of proteins and/or phosphoproteins (e.g. Akt, pAkt, mTOR and p-mTOR) related to the IGF2 signal pathway in the CA1. These results demonstrate that the overexpression of SIRT6 in the CA1 impaired the formation of long-term fear memory, and SIRT6 in the CA1 may negatively modulate the formation of contextual fear memory via inhibiting the IGF signaling pathway. Nature Publishing Group 2016-01-06 /pmc/articles/PMC4702175/ /pubmed/26732053 http://dx.doi.org/10.1038/srep18982 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Yin, Xi Gao, Yuan Shi, Hai-Shui Song, Li Wang, Jie-Chao Shao, Juan Geng, Xu-Hong Xue, Gai Li, Jian-Li Hou, Yan-Ning
spellingShingle	Yin, Xi Gao, Yuan Shi, Hai-Shui Song, Li Wang, Jie-Chao Shao, Juan Geng, Xu-Hong Xue, Gai Li, Jian-Li Hou, Yan-Ning Overexpression of SIRT6 in the hippocampal CA1 impairs the formation of long-term contextual fear memory
author_facet	Yin, Xi Gao, Yuan Shi, Hai-Shui Song, Li Wang, Jie-Chao Shao, Juan Geng, Xu-Hong Xue, Gai Li, Jian-Li Hou, Yan-Ning
author_sort	Yin, Xi
title	Overexpression of SIRT6 in the hippocampal CA1 impairs the formation of long-term contextual fear memory
title_short	Overexpression of SIRT6 in the hippocampal CA1 impairs the formation of long-term contextual fear memory
title_full	Overexpression of SIRT6 in the hippocampal CA1 impairs the formation of long-term contextual fear memory
title_fullStr	Overexpression of SIRT6 in the hippocampal CA1 impairs the formation of long-term contextual fear memory
title_full_unstemmed	Overexpression of SIRT6 in the hippocampal CA1 impairs the formation of long-term contextual fear memory
title_sort	overexpression of sirt6 in the hippocampal ca1 impairs the formation of long-term contextual fear memory
description	Histone modifications have been implicated in learning and memory. Our previous transcriptome data showed that expression of sirtuins 6 (SIRT6), a member of Histone deacetylases (HDACs) family in the hippocampal cornu ammonis 1 (CA1) was decreased after contextual fear conditioning. However, the role of SIRT6 in the formation of memory is still elusive. In the present study, we found that contextual fear conditioning inhibited translational expression of SIRT6 in the CA1. Microinfusion of lentiviral vector-expressing SIRT6 into theCA1 region selectively enhanced the expression of SIRT6 and impaired the formation of long-term contextual fear memory without affecting short-term fear memory. The overexpression of SIRT6 in the CA1 had no effect on anxiety-like behaviors or locomotor activity. Also, we also found that SIRT6 overexpression significantly inhibited the expression of insulin-like factor 2 (IGF2) and amounts of proteins and/or phosphoproteins (e.g. Akt, pAkt, mTOR and p-mTOR) related to the IGF2 signal pathway in the CA1. These results demonstrate that the overexpression of SIRT6 in the CA1 impaired the formation of long-term fear memory, and SIRT6 in the CA1 may negatively modulate the formation of contextual fear memory via inhibiting the IGF signaling pathway.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702175/
_version_	1613520340933148672

Overexpression of SIRT6 in the hippocampal CA1 impairs the formation of long-term contextual fear memory

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