Sirt1 ameliorates chronic mild unpredictable stress-induced depression-like behaviors in mice by promoting hippocampal microglia M2 polarization

Abstract

Objective To explore the effect of silent mating-type information regulation 2 homolog 1 (Sirt1) on depression-like behaviors in mice and the underlying molecular mechanism. Methods Forty 8-week-old male C57BL/6 mice were subjected to chronic mild unpredictable stress (CUMS) to establish models of depression. The mouse models were randomized equally into CUMS group(n=20) and CUMS+Sirt1 group(n=20), and the mice in the latter group were injected with 5 μmol SRT2104, a Sirt1 agonist, in the bilateral hippocampus. With another 20 mice without CUMS as the control group, the mice in the 2 CUMS groups were evaluated for depression-like behaviors; the hippocampal microglia number and phenotypes in the mice were assessed by immunofluorescence staining and flow cytometry, and Western blotting was used to detect the expression of Sirt1, P-GSK3β and P-PTEN in the hippocampus. Results Compared with those in CUMS group, the mice in CUMS+Sirt1 group showed a significantly increased sucrose preference (P 0.05), the number of M1 phenotype microglia was decreased and that of M2 phenotype microglia was increased significantly in CUMS+Sirt1 group (P < 0.01); the expression of Sirt1, P-GSK3β and P-PTEN in the hippocampus were increased significantly in CUMS+Sirt1 group compared 2 those in CUMS group (P < 0.01). Conclusion Sirt1 ameliorates CUMS-induced depression-like behaviors in mice by promoting the transformation of microglia into M2 phenotype.

Keywords

• depression
• silent mating-type information regulation 2 homolog 1
• microglia
• gsk3β/pten