Up-regulation of SIRT6 in the hippocampus induced rats with depression-like behavior via the block Akt/GSK3β signaling pathway

作者：Mao, Qiang; Gong, Xue; Zhou, Chanjuan; Tu, Zhe; Zhao, Libo; Wang, Ling; Wang, Xinfa; Sun, Lu; Xia, Jinjun; Lian, Bin; Chen, Jianjun; Mu, Jun; Yang, Deyu; Xie, Peng^*

来源：Behavioural Brain Research, 2017, 323: 38-46.

DOI：10.1016/j.bbr.2017.01.035

• Depression
• Chronic unpredicted mild stress
• CUMS
• Hippocampus
• Neuron
• SIRT6
• Lentivirus
• Akt-GSK3 beta
• Signaling pathway

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 pocr, p-AKT, P-GSK3 beta, decreased the ratios of p-GSK3 beta/GSK3 beta 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-GSK3 beta signaling.

• 出版日期2017-4-14
• 单位重庆医科大学