title: Up-regulation of SIRT6 in the hippocampus induced rats with depression-like behavior via the block Akt/GSK3β signaling pathway.
abstract: Major depression is the leading cause of disability worldwide, which is associated with diverse alterations in brain such as neuro-inflammation, synaptic dysfunction, and cognitive deficit. Accumulating evidences suggest sirtuins (SIRTs) are involved in brain developmental disorders, metabolic diseases and play a key role in cognition and synaptic plasticity, yet the role in mood regulation remains controversial. Hence, Western blotting and RT-qPCR were used to investigate whether SIRTs (SIRT1-7) expression levels were altered in the hippocampus of rats, which followed 5 weeks of chronic unpredictable mild stress (CUMS) treatment, the results showed depressive-like behaviors: like body weight, forced swim test and sucrose preference test and SIRT6 was a significant increase in the hippocampal of CUMS rats. Furthermore, via a lentivirus-mediated transfection in hippocampal neurons, we aimed to detect how SIRT6 influence the function of hippocampus. The SIRT6 overexpression significantly inhibited expressions of proteins and/or phosphoproteins (e.g AKT, p-AKT, P-GSK3β), decreased the ratios of p-GSK3β/GSK3β and p-Akt/Akt in the primary hippocampus neurons. Thus, our data indicates that SIRT6 is involved in the modulation of depressive-like behaviors and affects the survival and synaptic plasticity of hippocampal neuron via inhibitory activation of Akt-GSK3β signaling.
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China; Department of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing 400016, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Mao
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China; Department of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing 400016, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing 400016, China.
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China; Department of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing 400016, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Tu
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing 400016, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing 400016, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing 400016, China.
authors.forename: Xinfa
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing 400016, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing 400016, China.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Xia
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing 400016, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lian
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing 400016, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing 400016, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Mu
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China; Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing 400016, China.
authors.forename: Deyu
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China; Department of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing 400016, China. Electronic address: xiepeng@cqmu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
mesh_terms: D000818:Animals; D003865:Major Depressive Disorder / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism*; D040901:Proteomics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D037761:Sirtuins / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D037761:Sirtuins; C560607:sirtuin 6, rat
keywords: Akt-GSK3β; CUMS; Chronic unpredicted mild stress; Depression; Hippocampus; Lentivirus; Neuron; SIRT6; Signaling pathway