Liru Dong1,2, Songjun Wang1, Yingmin Li1, Ziqin Zhao3, Yiwen Shen3, Li Liu4, Guangming Xu1, Chunling Ma1, Shujin Li1, Xiaojing Zhang1, Bin Cong1. 1. Department of Forensic Medicine, Basic Medical College, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang, China. 2. Department of Pathology, Affiliated Hospital of North China University of Science and Technology, Tangshan, China. 3. Department of Forensic Medcine, School of Basic Medical Sciences, Fudan University, Shanghai, China. 4. Forensic Science Service of the Beijing Public Security Bureau, Beijing, China.
Abstract
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 β-subunit of S100 (S100β) 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 S100β 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, S100β, 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, anti-apoptosis and astrocyte increasing effects.
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 β-subunit of S100 (S100β) 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 S100β 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, S100β, 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, anti-apoptosis and astrocyte increasing effects.