脑卒中后抑郁大鼠额前皮质小胶质细胞表达BDNF及其受体TrkB

目的:探讨脑卒中后抑郁(post-stroke depression,PSD)大鼠额前皮质小胶质细胞表达脑源性神经营养因子(BDNF)及其高亲和力受体酪氨酸激酶受体B(TrkB)的情况,了解小胶质细胞在PSD发病机制中的作用。方法:将健康成年SD大鼠随机分为正常组、抑郁组、脑卒中组和PSD组,每组10只。卒中组采用线栓法建立局灶性脑缺血模型;抑郁组采用慢性不可预见的中等应激刺激(CUMS)结合孤养法建立大鼠慢性应激抑郁模型;PSD组采用线栓法建立局灶性脑缺血模型后,再加以CUMS及孤养法建立PSD大鼠模型。于造模后第29 d(4周后)及第57 d(8周后)应用免疫荧光双标染色法检测各组大鼠额前皮质小胶质细胞表达BDNF及其高亲和力受体TrkB的情况。结果:造模后第29 d PSD组额前皮质OX42(小胶质细胞标记物)与BDNF免疫荧光双标阳性细胞及与TrkB免疫荧光双标阳性细胞平均光密度值均最小,正常对照组均最大。单因素方差分析结果显示:PSD组与各对照组(抑郁组、脑卒中组、正常组)相比,差异均有统计学意义(P0.05);抑郁组及脑卒中组均较正常对照组小(P0.05)。造模后第57 d PSD组额前皮质OX42与BDNF免疫荧光双标阳性细胞及OX42与TrkB免疫荧光双标阳性细胞平均光密度值均为最小,正常对照组均最大。PSD组与各对照组(抑郁组、脑卒中组、正常组)相比,差异均有统计学意义(P0.05);抑郁组也较正常对照组小(P0.05);脑卒中组也较正常对照组小(P0.05);抑郁组与脑卒中组相比,差异无统计学意义(P0.05)。结论:PSD大鼠额前皮质小胶质细胞表达BDNF及TrkB,其平均光密度值在PSD急性期及慢性期均明显减少,可能与PSD发病机制相关。小胶质细胞可能通过减少BDNF及其高亲和力受体TrkB的表达在PSD发病过程中发挥了重要的作用。

The expression of BDNF and TrkB of the microglia in prefrontal cortex of post-stroke depression rats

Objective:To investigate the expression of brain-derived neuro-trophic factor (BDNF) and the high af finity receptor tyrosine kinase receptor B (TrkB) of the microglia,in the prefrontal cortex-post-stroke depression in rats.To understand the role of microglia in the pathogenesis of PSD.Methods:40 healthy adult SD rats were divided into normal group,depression group,stroke group and PSD group randomly,distributing 10 rats into each group.In the stroke group,focal cerebral ischemia rat models were established by sutural vascular occlusion.In the depression group,rat models were induced depression by chronic unpredictable mild stress stimulation (CUMS) and separate breeding.In the PSD group,rat models were induced with focal cerebral ischemia by sutural vascular occlusion firstly,then with comprehensive chronic unpredictable mild stress (CUMS) and were bread separately on this basis.Expression of BDNF and TrkB double immunofluorescent positive cells,of the microglia in prefrontal cortex was detected by staining on day 29 (4 weeks) and 57 (8 weeks) respectively.Results:On day 29,the average optical density levels of the double labeled OX42 (microglia marker) with BDNF or TrkB in prefrontal cortex of the PSD group were the lowest;while in the normal group were the highest.One way ANOVA analysis showed:compared with the control group (depression group,stroke group and normal group),there were significant changes in the levels of expression of BDNF and TrkB double immunofluorescent positive cells,such as:of the PSD group were significantly lower (P ＜ 0.05).The depression group and stroke group were lower than the normal control group (P ＜ 0.05).On day 57,double immuno fluorescence,the average levels of optical density of prefrontal cortex OX42 (microglia marker) of expression of BDNF and TrkB positive cells of the PSD group were lowest,while in the normal group were the highest.Compared with the control group (depression group,stroke group,and normal group),expression of BDNF and TrkB double immunefluorescent positive cells,of the PSD group were significantly lower (P ＜ 0.05).The depression group was lower than the normal group (P ＜ 0.05).The stroke group were lower than the normal control group (P ＜ 0.05).Between the depression group and the stroke group,the difference was not statistically significant (P ＞ 0.05).Conclusion:The average levels of optical density value at prefrontal cortex OX42 (microglia marker) of expression of BDNF and TrkB double immunefluorescent positive cells,in the PSD rats during acute stage and chronic stage were reduced significantly,this may be associated with the pathogenesis of PSD.Thus,decreasing Microglia,the expression of BDNF and its high affinity receptor TrkB,may play an important role in the pathogenesis of PSD.