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

To study the effects of exogenous glucocorticoids on the structure and function of gap junctions in the prefrontal cortex (PFC) of rats, and to investigate the effects of the glucocorticoid receptor (GR) inhibitor mifepristone on the actions of glucocorticoids. The glucocorticoid level in rats was increased by subcutaneous injection of corticosterone (CORT), and mifepristone was administered by gavage to block GR. The degree of sucrose consumption in rats was measured to evaluate the anhedonic state of rats. The function and ultrastructural changes of gap junctions in astrocytes in the PFC region were analyzed by Lucifer yellow dye tracing and electron microscopy methods, and the expression of connexin 43 (Cx43) was detected by immunofluorescence method. The results showed that subcutaneous injection of CORT induced a decrease in sucrose consumption in rats, a shortening of the diffusion distance of Lucifer yellow in the PFC region, a reduction in cell-cell coupling, an incomplete structure of gap junctions in astrocytes, a widening of the gap, and a decrease in the number of immunopositive dots of Cx43. Mifepristone reversed all of these changes. The above results indicate that mifepristone can improve the damage to the function and structure of gap junctions in astrocytes in the PFC region of rats with depression-like symptoms induced by an increase in exogenous glucocorticoid levels. The damage to the communication function of gap junctions in astrocytes may be related to the activation of GR.

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。