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

Yue WANG; Tengfei WAN; Chunmei DUAN; Li WANG; Xiaoyan CHEN

doi:10.16016/j.1000-5404.201901077

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

Basic Medicine | 更新时间：2026-01-09

- Sirt1 ameliorates chronic mild unpredictable stress-induced depression-like behaviors in mice by promoting hippocampal microglia M2 polarization
- Journal of Third Military Medical University Vol. 41, Issue 14, Pages: 1301-1307(2019)
- 作者机构：
  
  1.400037 重庆，陆军军医大学(第三军医大学)第二附属医院神经内科
  2.110016 沈阳，北部战区总医院干一科
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(81701123)
- DOI：10.16016/j.1000-5404.201901077
  CLC： R345.1;R363.27;R749.4
- Received：10 January 2019，
  
  Revised：2019-03-04，
  
  Published：30 July 2019
- 稿件说明：
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Yue WANG, Tengfei WAN, Chunmei DUAN, et al. Sirt1 ameliorates chronic mild unpredictable stress-induced depression-like behaviors in mice by promoting hippocampal microglia M2 polarization[J]. Journal of Third Military Medical University, 2019, 41(14): 1301-1307.
DOI：

Yue WANG, Tengfei WAN, Chunmei DUAN, et al. Sirt1 ameliorates chronic mild unpredictable stress-induced depression-like behaviors in mice by promoting hippocampal microglia M2 polarization[J]. Journal of Third Military Medical University, 2019, 41(14): 1301-1307. DOI： 10.16016/j.1000-5404.201901077.

摘要

目的

探讨沉默信息调节因子2相关酶1 (silent mating-type information regulation 2 homolog 1

Sirt1)对小鼠抑郁样行为的影响以及相关的分子机制。

方法

共纳入60只8周龄C57BL/6雄性小鼠，利用慢性温和不可预知性应激(chronic mild unpredictable stress，CUMS)建立抑郁症小鼠模型。实验分为Control组(

=20)、CUMS组(

=20)和CUMS+Sirt1组(

=20，小鼠双侧海马注射Sirt1激动剂SRT2104各5 μmol)。采用行为学、免疫荧光、流式细胞术以及Western blot等方法，对小鼠的抑郁样行为、小胶质细胞表型、GSK3β/PTEN信号通路进行检测。

结果

与CUMS组比较，CUMS+Sirt1组小鼠对糖水的偏好程度明显增加(

＜0.01)，同时在强迫游泳实验与悬尾实验中的不动时间明显降低(

＜0.01)；与CUMS组比较，虽然CUMS+Sirt1组小鼠脑内总的小胶质细胞数量无显著变化

但脑内的M1型小胶质细胞数量明显减少(

＜0.01)，M2型小胶质细胞数量明显增加(

＜0.01)，M1/M2的比率也明显减少(

＜0.01)；相对于CUMS组，CUMS+Sirt1组小鼠海马中Sirt1、P-GSK3β和P-PTEN蛋白表达也显著增高

(

＜0.01)。

结论

Sirt1通过促进抑郁症小鼠模型海马中的小胶质细胞向M2型转化进而改善小鼠的抑郁样行为。

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(

=20) and CUMS+Sirt1 group(

=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 (

0.01) with obviously decreased immobility time in forced swimming test (

0.01) and tail suspension test (

0.01). Although the number of hippocampal microglia did not differ significantly between the 2 CUMS groups (

0.05)

the number of M1 phenotype microglia was decreased and that of M2 phenotype microglia was increased significantly in CUMS+Sirt1 group (

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 (

0.01).

Conclusion

Sirt1 ameliorates CUMS-induced depression-like behaviors in mice by promoting the transformation of microglia into M2 phenotype.

关键词

Keywords

references

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