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

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机构: [1]Department of Functional region of Diagnosis, Hebei Medical University Fourth Hospital, Hebei Medical University,Shijiazhuang 050011, China [2]Department of Biochemistry and Molecular Biology, College of basic medicine,Hebei Medical University, Shijiazhuang 050017, China [3]Department of vasculocardiology, Hebei Province GeriatricHospital, Shijiazhuang, 050011, China [4]Department of Senile Disease, the Third Hospital of Hebei MedicalUniversity, Shijiazhuang 050000, China [5]Department of Pharmacy, the Bethune International Peace Hospital ofPLA, Shijiazhuang 050082, China
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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 the CA1 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.

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出版当年[2016]版:
大类 | 2 区 综合性期刊
小类 | 2 区 综合性期刊
最新[2025]版:
大类 | 3 区 综合性期刊
小类 | 3 区 综合性期刊
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出版当年[2016]版:
Q1 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

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第一作者机构: [1]Department of Functional region of Diagnosis, Hebei Medical University Fourth Hospital, Hebei Medical University,Shijiazhuang 050011, China
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通讯机构: [2]Department of Biochemistry and Molecular Biology, College of basic medicine,Hebei Medical University, Shijiazhuang 050017, China [5]Department of Pharmacy, the Bethune International Peace Hospital ofPLA, Shijiazhuang 050082, China
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