Elevated glucocorticoid damages gap junction structure and function in rat prefrontal cortex
10.16438/j.0513-4870.2018-0436
- VernacularTitle:糖皮质激素水平升高损伤大鼠前额皮层缝隙连接结构和功能
- Author:
Yu-xia LOU
1
;
Jing LI
2
;
Cong-yuan XIA
2
;
Zhen-zhen WANG
2
;
Nai-hong CHEN
1
Author Information
1. Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
2. State Key Laboratory of Bioactive Substances and Functions of Natural Medicine, Neuroscience Center, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
gap junction;
mifepristone;
prefrontal cortex;
glucocorticoid;
depression
- From:
Acta Pharmaceutica Sinica
2018;53(10):1645-1651
- CountryChina
- Language:Chinese
-
Abstract:
In this article, we exogenously administered glucocorticoids to rats, observed changes in the structure and function of gap junctions in the prefrontal cortex (PFC) and studied the effects of glucocorticoid receptor (GR) inhibitor mifepristone on these changes. Subcutaneous injection of corticosterone (CORT) was used to increase glucocorticoid levels in rats, intragastric administration of mifepristone antagonist GR. Sucrose preference test was conducted to evaluate anhedonia. Dye transfer assay and electron microscopy were used to analyze the function and ultrastructural changes of gap junctions in astrocytes of PFC. Immunofluorescence was used to detect the expression of connexin 43 (Cx43). Animals exposed to CORT showed behavioral deficits in sucrose preference test, exhibited significant decreases in diffusion of gap junction channel-permeable dye and abnormal gap junctional ultrastructure, as well as reductions in Cx43 puncta density in the PFC. The behavioral and cellular alterations induced by CORT were reversed or blocked by treatment with the GR antagonist mifepristone. The results suggest that mifepristone can improve the gap junction function and structural damage of astrocytes in the PFC of depressive rats induced by CORT. In conclusion, the activation of the GR receptor may contribute to gap junction dysfunction in the PFC.
