title: Overexpression of SIRT6 in the hippocampal CA1 impairs the formation of long-term contextual fear memory.
abstract: 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.
authors.affiliation: Department of Functional region of Diagnosis, Hebei Medical University Fourth Hospital, Hebei Medical University, Shijiazhuang 050011, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Biochemistry and Molecular Biology, College of basic medicine, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Biochemistry and Molecular Biology, College of basic medicine, Hebei Medical University, Shijiazhuang 050017, China.|Department of Pharmacy, the Bethune International Peace Hospital of PLA, Shijiazhuang 050082, China.
authors.forename: Hai-Shui
authors.initials: HS
authors.lastname: Shi
authors.affiliation: Department of Biochemistry and Molecular Biology, College of basic medicine, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of vasculocardiology, Hebei Province Geriatric Hospital, Shijiazhuang, 050011, China.
authors.forename: Jie-Chao
authors.initials: JC
authors.lastname: Wang
authors.affiliation: Department of Senile Disease, the Third Hospital of Hebei Medical University, Shijiazhuang 050000, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Shao
authors.affiliation: Department of Functional region of Diagnosis, Hebei Medical University Fourth Hospital, Hebei Medical University, Shijiazhuang 050011, China.
authors.forename: Xu-Hong
authors.initials: XH
authors.lastname: Geng
authors.affiliation: Department of Pharmacy, the Bethune International Peace Hospital of PLA, Shijiazhuang 050082, China.
authors.forename: Gai
authors.initials: G
authors.lastname: Xue
authors.affiliation: Department of Pharmacy, the Bethune International Peace Hospital of PLA, Shijiazhuang 050082, China.
authors.forename: Jian-Li
authors.initials: JL
authors.lastname: Li
authors.affiliation: Department of Pharmacy, the Bethune International Peace Hospital of PLA, Shijiazhuang 050082, China.
authors.forename: Yan-Ning
authors.initials: YN
authors.lastname: Hou
mesh_terms: D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D003213:Conditioning, Psychological; D005239:Fear; D015870:Gene Expression; D020869:Gene Expression Profiling; D018014:Gene Transfer Techniques; D008297:Male; D057567:Memory, Long-Term; D009043:Motor Activity; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D037761:Sirtuins / Q000235:genetics* / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D013002:Somatomedins; D051057:Proto-Oncogene Proteins c-akt; D037761:Sirtuins; C560607:sirtuin 6, rat