RU486 Reverses Emotional Disorders by Influencing Astrocytes and Endoplasmic Reticulum Stress in Chronic Restraint Stress Challenged Rats
RU486 Reverses Emotional Disorders by Influencing Astrocytes and Endoplasmic Reticulum Stress in Chronic Restraint Stress Challenged Rats
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RU486 通过影响慢性束缚应激大鼠的星形胶质细胞和内质网应激来逆转情绪障碍。
DOI：
10.1159/000478764
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Cong, Bin
中科院分区：
文献类型：
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作者：
Dong, Liru;Wang, Songjun;Cong, Bin
目的：研究米非司酮对慢性束缚应激大鼠情绪障碍的影响，并探讨其作用机制。研究方法：为此，将80只健康雄性Sprague道利大鼠随机分为4组：正常组（Con组，Con组成员不接受任何治疗，自由饮食），慢性束缚应激组CRS组：正常Sprague道利大鼠，慢性束缚应激，6h/d，共21天;丙二醇基团（CRS+丙二醇）和RU 486基团（CRS + RU 486）。每次CRS手术前30分钟给予RU 486或丙二醇。CRS暴露后24小时，我们使用高架十字迷宫（ELS）研究CRS对焦虑样行为的影响。为探讨RU486抗焦虑作用的机制，采用免疫组化和Western blot方法检测了大鼠海马神经元胶质细胞酸性蛋白（GFAP）和S100 β亚基（S100 β）的表达。流式细胞仪检测细胞凋亡。此外，采用Western blot方法检测内质网应激标志物葡萄糖调节蛋白78（GRP78）、C/EBP同源蛋白（CHOP）和半胱氨酸天冬氨酸特异性蛋白酶-12（Caspase-12）。结果如下：与对照组相比，CRS和丙二醇组的大鼠在开放臂上的探索行为减少，并且这些减少伴随着杏仁核中GFAP和S100 β表达的显著减少，细胞凋亡和GRP78，CHOP和caspase-12表达的增加。然而，RU 486增加了探索行为，逆转了GFAP、S100 β、GRP 78、CHOP和caspase-12的变化，并保护细胞免受凋亡。结论：总之，这些数据表明，暴露于慢性束缚应激减少星形胶质细胞的数量，并诱导杏仁核中的细胞凋亡和ER应激，这可能是精神疾病的原因。RU486能显著改善CRS诱导的焦虑模型大鼠的异常行为。RU486的保护作用可能与其抗ER应激、抗凋亡和促进星形胶质细胞增殖有关。(C)2017作者由S.发布Karger AG，巴塞尔
Aims: To investigate the effect of RU486 (mifepristone) on emotional disorders in chronic restraint stress-induced rats and to explore the mechanisms of that phenomenon. Methods: For this purpose, 80 healthy male Sprague Dawley rats were randomly divided into four groups: the normal group (Con group, The Con group members received no treatment, eating and drinking freely), the chronic restraint stress group (CRS group, normal Sprague Dawley rats treated with chronic restraint stress, 6 h/day for 21days), the propylene glycol group (CRS+ propylene glycol) and the RU486 group (CRS+ RU486). RU486 or propylene glycol was administered 30 mins before each CRS procedure. Twenty-four hours after CRS exposure, we investigated the effects of CRS on the anxiety-like behavior using an elevated plus-maze (EPM). To explore the mechanisms of RU486 on anxiety, we measured the expression of glial fibrillary acid protein (GFAP) and beta-subunit of S100 (S100 beta) via immunohistochemistry and western blot analysis. Apoptosis was demonstrated by flow cytometry. In addition, endoplasmic reticulum (ER) stress markers, glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and Cysteine aspartic acid specific protease-12 (Caspase-12), were detected by western blot analysis. Results: Compared to the control group, rats in the CRS and propylene glycol group showed decreased exploratory behavior on the open arms during EPM testing, and these reductions were accompanied by significantly reduced GFAP and S100 beta expression, increased apoptosis and GRP78, CHOP, and caspase-12 expression in the amygdala. However, RU486 increases the exploratory behavior and reverses the changes of GFAP, S100 beta, GRP78, CHOP, and caspase-12 and protects cells against apoptosis. Conclusions: Taken together, these data suggest that exposure to chronic restraint stress decreases the number of astrocytes and induces apoptosis and ER stress in the amygdala, which are possible causes for psychiatric disorders. RU486 can significantly ameliorate abnormal behaviors in CRS-induced anxiety model rats. The protective effects of RU486 could be attributed to its anti-ER stress, antiapoptosis and astrocyte increasing effects. (C) 2017 The Author(s) Published by S. Karger AG, Basel