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[自愿性轮转运动通过STAT3信号通路调节海马小胶质细胞极化以抑制大鼠慢性应激诱导的抑郁样行为]

[Voluntary wheel running exercise regulates microglia polarization in hippocampus through STAT3 signal pathway to inhibit depression-like behavior induced by chronic stress in rats].

作者信息

Luo Jie, Wang Jing-Qiong, Xie Li-Na, Meng An-Na, Zheng Si-Si, Zhou Shou-Hong

机构信息

College of Physical Education, Hunan First Normal College, Changsha 410205, China.

Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin 541199, China.

出版信息

Sheng Li Xue Bao. 2022 Apr 25;74(2):177-187.

PMID:35503065
Abstract

This paper was aimed to investigate the effect of voluntary wheel running exercise on depression-like behavior induced by chronic water immersion restraint stress (CWIRS) and the underlying mechanism. Sprague-Dawley (SD) rats received CWIRS to induce depression-like behavior and 4-week voluntary wheel running exercise. Meanwhile, the rats were treated with lipopolysaccharide (LPS) or STAT3 over-expression vector (pcDNA-STAT3) by intracerebroventricular injection. Behavioral tests were used to detect depression-like behavior. ELISA assay was used to detect levels of various inflammatory factors in the rat hippocampus. Western blot was used to detect protein expression levels of ionized calcium binding adaptor molecule 1 (Iba1), inducible nitric oxide synthase (iNOS), arginase 1 (Arg1), phosphorylated STAT3 (p-STAT3) and total STAT3 (t-STAT3). The results showed that, compared with stress group, stress + exercise group exhibited improved depression-like behavior, decreased interleukin-1β (IL-1β) and IL-6 levels, increased IL-4 and IL-10 levels, down-regulated Iba-1 and iNOS protein expression levels, up-regulated Arg1 protein expression level, and decreased p-STAT3/t-STAT3 ratio in hippocampal tissue. LPS reversed the improving effect of voluntary wheel running exercise on depression-like behavior in rats, and the over-expression of STAT3 reversed the promoting effects of voluntary wheel running on M2 polarization of microglial cells in rat hippocampus and depression-like behavior. These results suggest that voluntary wheel running ameliorates the depression-like behavior induced by CWIRS in rats, and the mechanism may be related to regulating hippocampal microglia polarization via STAT3 signaling pathway.

摘要

本文旨在研究自愿轮转运动对慢性水浸束缚应激(CWIRS)诱导的抑郁样行为的影响及其潜在机制。将Sprague-Dawley(SD)大鼠进行CWIRS以诱导抑郁样行为,并进行4周的自愿轮转运动。同时,通过脑室内注射给予大鼠脂多糖(LPS)或STAT3过表达载体(pcDNA-STAT3)。采用行为学测试检测抑郁样行为。采用ELISA法检测大鼠海马中各种炎症因子的水平。采用蛋白质免疫印迹法检测离子钙结合衔接分子1(Iba1)、诱导型一氧化氮合酶(iNOS)、精氨酸酶1(Arg1)、磷酸化STAT3(p-STAT3)和总STAT3(t-STAT3)的蛋白表达水平。结果显示,与应激组相比,应激+运动组的抑郁样行为得到改善,白细胞介素-1β(IL-1β)和IL-6水平降低,IL-4和IL-10水平升高,海马组织中Iba-1和iNOS蛋白表达水平下调,Arg1蛋白表达水平上调,p-STAT3/t-STAT3比值降低。LPS逆转了自愿轮转运动对大鼠抑郁样行为的改善作用,STAT3的过表达逆转了自愿轮转运动对大鼠海马小胶质细胞M2极化和抑郁样行为的促进作用。这些结果表明,自愿轮转运动可改善CWIRS诱导的大鼠抑郁样行为,其机制可能与通过STAT3信号通路调节海马小胶质细胞极化有关。

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