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[PMID]: | 28662512 |
[Au] Autor: | Dong L; Wang S; Li Y; Zhao Z; Shen Y; Liu L; Xu G; Ma C; Li S; Zhang X; Cong B |
[Ad] Endereço: | Department of Forensic Medicine, Basic Medical College, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang, China. |
[Ti] Título: | RU486 Reverses Emotional Disorders by Influencing Astrocytes and Endoplasmic Reticulum Stress in Chronic Restraint Stress Challenged Rats. |
[So] Source: | Cell Physiol Biochem;42(3):1098-1108, 2017. | [Is] ISSN: | 1421-9778 |
[Cp] País de publicação: | Switzerland |
[La] Idioma: | eng |
[Ab] Resumo: | 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 ß-subunit of S100 (S100ß) 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 S100ß 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, S100ß, 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. |
[Mh] Termos MeSH primário: |
Ansiedade/tratamento farmacológico Astrócitos/efeitos dos fármacos Estresse do Retículo Endoplasmático/efeitos dos fármacos Antagonistas de Hormônios/uso terapêutico Mifepristona/uso terapêutico Estresse Psicológico/tratamento farmacológico
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[Mh] Termos MeSH secundário: |
Tonsila do Cerebelo/efeitos dos fármacos Tonsila do Cerebelo/metabolismo Tonsila do Cerebelo/patologia Animais Ansiedade/metabolismo Ansiedade/patologia Astrócitos/metabolismo Astrócitos/patologia Proteína Glial Fibrilar Ácida/análise Proteína Glial Fibrilar Ácida/metabolismo Masculino Ratos Sprague-Dawley Subunidade beta da Proteína Ligante de Cálcio S100/análise Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo Estresse Psicológico/metabolismo Estresse Psicológico/patologia
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Glial Fibrillary Acidic Protein); 0 (Hormone Antagonists); 0 (S100 Calcium Binding Protein beta Subunit); 0 (S100b protein, rat); 0 (glial fibrillary acid protein, rat); 320T6RNW1F (Mifepristone) |
[Em] Mês de entrada: | 1711 |
[Cu] Atualização por classe: | 171107 |
[Lr] Data última revisão:
| 171107 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170630 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1159/000478764 |
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