[1]王玥,万腾飞,段春梅,等.Sirt1通过促进海马中小胶质细胞向M2型转化改善慢性温和不可预知性应激模型小鼠的抑郁样行为[J].第三军医大学学报,2019,41(14):1301-1307.
 WANG Yue,WAN Tengfei,DUAN Chunmei,et al.Sirt1 ameliorates chronic mild unpredictable stress-induced depression-like behaviors in mice by promoting hippocampal microglia M2 polarization[J].J Third Mil Med Univ,2019,41(14):1301-1307.
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Sirt1通过促进海马中小胶质细胞向M2型转化改善慢性温和不可预知性应激模型小鼠的抑郁样行为(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
41卷
期数:
2019年第14期
页码:
1301-1307
栏目:
基础医学
出版日期:
2019-07-30

文章信息/Info

Title:
Sirt1 ameliorates chronic mild unpredictable stress-induced depression-like behaviors in mice by promoting hippocampal microglia M2 polarization
作者:
王玥万腾飞段春梅王礼陈晓燕
陆军军医大学(第三军医大学)第二附属医院神经内科;北部战区总医院干一科
Author(s):

Department of Neurology, Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037; First Cadre Ward, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, 110016, China

关键词:
抑郁症沉默信息调节因子2相关酶1小胶质细胞GSK3&beta/PTEN
Keywords:
depression silent mating-type information regulation 2 homolog 1 microglia GSK3&beta/PTEN
分类号:
R345.1;R363.27;R749.4
文献标志码:
A
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(n=20)、CUMS组(n=20)和CUMS+Sirt1组(n=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(P<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(P<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(P<0.01),M2型小胶质细胞数量明显增加(P<0.01),M1/M2的比率也明显减少(P<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(P<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(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<0.01) with obviously decreased immobility time in forced swimming test (P<0.01) and tail suspension test (P<0.01). Although the number of hippocampal microglia did not differ significantly between the 2 CUMS groups (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.
 

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更新日期/Last Update: 2019-07-22