Glucocorticoid receptor activation induces decrease of hippocampal astrocyte number in rats

Glucocorticoid receptor activation induces decrease of hippocampal astrocyte number in rats
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糖皮质激素受体激活导致大鼠海马星形胶质细胞数量减少

DOI:
10.1007/s00213-018-4936-2
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发表时间:
2018-08
期刊:
影响因子:
3.4
通讯作者:
Chen Nai-Hong
Chen Nai-Hong
中科院分区:
医学3区
文献类型:
--
作者:
Lou Yu-Xia;Li Jing;Wang Zhen-Zhen;Xia Cong-Yuan;Chen Nai-Hong

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RationaleThe decrease of astrocyte number and hypothalamic-pituitary-adrenal (HPA) axis overactivity are observed in individuals with major depressive disorder. Elevated levels of glucocorticoids induced by hyperactivation of the HPA axis may result in glucocorticoid receptor (GR) activation. However, it is unclear whether there is a direct link between GR activation and the decrease of astrocyte number.MethodsAnimals were exposed to chronic unpredictable stress (CUS) for 28 days and treated with continuous subcutaneous injections of vehicle or corticosterone (CORT; 40 mg/kg/day) for 21 days. We then administered mifepristone on day 21 after CUS and on day 18 after the CORT treatment. We observed behavioral deficits in the sucrose preference test, open field test, and forced swim test. Protein expression was analyzed using immunofluorescence (IF) and western blot (WB).ResultsAnimals exposed to CUS exhibited behavioral deficits in tests measuring anhedonia, anxiety, and despair state. They also had decreases in glial fibrillary acidic protein (GFAP) expression and numbers of GFAP-positive cells in the hippocampus. The behavioral and cellular alterations induced by CUS were reversed by subchronic treatment with the GR antagonist mifepristone. We also found that the subcutaneous injection of glucocorticoids may induce depression-like behavior and reduce GFAP protein expression in rats, which was similarly reversed by mifepristone.ConclusionsThese findings provide experimental evidence that GR activation due to elevated CORT levels induces the decrease of hippocampal astrocyte number in rats.
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