Glucocorticoid receptor activation induces decrease of hippocampal astrocyte number in rats
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The 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.
Animals 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).
Animals 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.
These findings provide experimental evidence that GR activation due to elevated CORT levels induces the decrease of hippocampal astrocyte number in rats.
KeywordsGFAP Glucocorticoid receptor Corticosterone Depression Astrocyte
This work was supported by the National Natural Science Foundation of China (81573636, 81773924, U1402221, 81560663), Beijing Natural Science Foundation (7182114), PUMC Youth Fund (3332016058), CAMS Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-004), the Scientific Research Foundation of the Higher Education Institutions of Hunan Province (15K091), Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study (BZ0150), PUMC Graduate Education and Teaching Reform Project (10023201600801), The State Key Laboratory Fund Open Project (GTZK201610), and China Postdoctoral Science Foundation (2013M540066).
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