表型
小胶质细胞
慢性应激
心理学
炎症
海马结构
抑郁症动物模型
神经科学
无血性
社会失败
高架加迷宫
促炎细胞因子
生物
作者
Chun-Mei Duan,Jian-Rong Zhang,Teng-Fei Wan,Yue Wang,Hui-Sheng Chen,Liang Liu
标识
DOI:10.1016/j.bbr.2019.112296
摘要
Although activated microglia-induced neuroinflammation link to the physiopathology of major depressive disorder, the homeostasis of switchable M1/M2 microglia in treating depression are unclear. Recent accumulating evidences suggest that Sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, plays a key role in mood regulation, yet its role in the polarization of microglia acting on depressive behaviors remains unknown. Here, we intended to investigate whether activation of SIRT1 in hippocampus has antidepressant potential in relation to microglial phenotypic switch. Chronic unpredictable mild stress (CUMS) treatment was performed on C57BL/6 mice, followed by injecting with SRT2104, a selective SIRT1 agonists. We found that activation of SIRT1 in hippocampus ameliorate CUMS-induced depressive-like behaviors, as indicated by sucrose preference test, tail suspension test and forced swim test. Moreover, activation of SIRT1 abrogated the increased expression of M1 markers (IL-6, IL-1β and iNOS,) and decreased expression of M2 markers (IL-10, TGF-β and Arignase1) induced by CUMS. Notably, activation of SIRT1 shifted microglia polarization toward the M2 phenotype in CUMS-induced depressive-like behaviors of mice. In addition, SRT2104 treatment ameliorated CUMS-induced SIRT1 decreased expression in the hippocampus coincides with the up-regulation phosphorylation levels of GSK3β and PTEN. Taken together, these findings indicated that activation of SIRT1 ameliorate CUMS-induced depressive-like behaviors via shifting microglial polarization toward the M2 phenotype, thereby providing a novel and beneficial therapeutic approach for depression that may be translatable to depression patients in the future.
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