药学学报, 2018, 53(10): 1645-1651
引用本文:
娄钰霞, 李婧, 夏聪媛, 王真真, 陈乃宏. 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[J]. 药学学报, 2018, 53(10): 1645-1651.
LOU Yu-xia, LI Jing, XIA Cong-yuan, WANG Zhen-zhen, CHEN Nai-hong. Elevated glucocorticoid damages gap junction structure and function in rat prefrontal cortex[J]. Acta Pharmaceutica Sinica, 2018, 53(10): 1645-1651.

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
娄钰霞1,2, 李婧2, 夏聪媛2, 王真真2, 陈乃宏1,2
1. 天津中医药大学, 天津 300193;
2. 中国医学科学院药物研究所, 神经科学中心, 天然药物活性物质与功能国家重点实验室, 北京 100050
摘要:
研究外源给予糖皮质激素对大鼠前额皮层(prefrontal cortex,PFC)缝隙连接结构和功能的影响,并研究糖皮质激素受体(glucocorticoid receptor,GR)抑制剂米非司酮对糖皮质激素作用的影响。通过皮下注射皮质酮(corticosterone,CORT)增加大鼠体内的糖皮质激素水平,灌胃给予米非司酮阻断GR。检测大鼠糖水消耗程度用以评价大鼠快感缺失状态。荧光黄染料示踪和电子显微镜方法分析PFC区星形胶质细胞缝隙连接的功能和超微结构变化,免疫荧光方法检测缝隙连接蛋白43(connexin 43,Cx43)的表达。结果显示,皮下注射CORT诱导大鼠糖水消耗降低,PFC区荧光黄扩散距离缩短,细胞间偶联减少,星形胶质细胞缝隙连接结构不完整,缝隙变宽,Cx43的免疫反应阳性点数降低。米非司酮均可逆转上述这些变化。以上结果表明,米非司酮可以改善外源糖皮质激素水平升高诱导的抑郁样大鼠PFC区星形胶质细胞缝隙连接功能和结构损伤。星形胶质细胞缝隙连接通讯功能的损伤可能与GR的激活有关。
关键词:    缝隙连接      米非司酮      前额皮层      糖皮质激素      抑郁症     
Elevated glucocorticoid damages gap junction structure and function in rat prefrontal cortex
LOU Yu-xia1,2, LI Jing2, XIA Cong-yuan2, WANG Zhen-zhen2, CHEN Nai-hong1,2
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
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.
Key words:    gap junction    mifepristone    prefrontal cortex    glucocorticoid    depression   
收稿日期: 2018-05-11
DOI: 10.16438/j.0513-4870.2018-0436
基金项目: 国家自然科学基金资助项目(81573636,81773924,U1402221,81560663);北京市自然科学基金资助项目(7182114);北京协和医学院“协和青年基金”资助项目(3332016058).
通讯作者: 陈乃宏,Tel/Fax:86-10-63165177,E-mail:chennh@imm.ac.cn
Email: chennh@imm.ac.cn
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