Parkinson病大鼠模型皮层纹状体末梢与纹状体黑质投射神经元之间突触的形态学变化

Parkinson病(PD)患者黑质多巴胺(DA)能神经元的丢失可能引发皮层纹状体通路活动的增强。但在皮层纹状体纤维与纹状体黑质神经元(D1R阳性)或纹状体苍白球神经元(D2R阳性)形成突触的连接中究竟是哪一类突触活动增强,目前尚不清楚。本研究用免疫电镜方法,在超微结构水平上观察了大鼠PD模型的损伤侧和正常侧纹状体内呈D1R或D2R阳性的神经元树突棘与皮层传入纤维末梢形成的不对称突触的形态学特征,对该突触以及其中的穿通型不对称突触的数量进行了定量观察。结果显示:损伤侧纹状体内呈D1R阳性的树突棘的穿通型不对称突触较正常侧增加了61%,但呈D2R阳性的树突棘的穿通型不对称突触数量却没有变化。表达D1R阳性的神经元参与的不对称突触后致密带的长度和突触前末梢的面积也有一定增加,而表达D2R阳性的神经元参与的不对称突触却未观察到此变化。以上结果表明:在损伤后,与基底神经节直接通路中呈D1R阳性的神经元相突触的皮层纹状体纤维非常活跃,这种使其活跃的机制可能对PD状态下的直接通路活动过低起一定的代偿作用。

THE MORPHOLOGICAL CHANGES IN THE SYNAPSES BETWEEN CORTICOSTRIATAL TERMINALS AND STRIATONIGRAL PROJECTION NEURONS IN THE RAT MODEL OF PARKINSON'S DISEASE

The loss of dopaminergic neurons in substantia nigra in Parkinson’s disease (PD) causes corticostriatal pathways becoming more active. It is not known, however, which type of the synapses become more active until now in the corticostriatal fibers make synapses with striatonigral neurons (D1R-positive) and striatopallidal neurons (D2R-positive). Using immuno electron microscopic method, the morphological characteristics of asymmetric synapses formed by cortical afferents fibers and terminals with the dendritic spines of D1R-positive or D2R-positive neurons in the striatum in the lesion side and the normal side in PD rat models were observed at ultrastructural level, and the number of synapses and perforated synapses among the synapses was performed a quantitative analysis. The results showed that in the striatum of the lesion side, a 61% increase in the number of perforated synapses making contact with D1R-positve dendritic spines was observed, whereas no change in the number of perforated synapses on D2R-positive spines was found. There was also a slight increase of the length of postsynaptic density and the area of presynaptic terminals in the asymmetric synapses making by D1R-positive dendritic spines, no such change was observed on the asymmetric synapses making by D2R-positive neurons. The above results suggest that the corticostriatal fibers in contact with D1R-positive neurons of the direct pathway of the basal ganglia become very active after lesion. The mechanism of making them active may have certain compensatory effect on the hypoactivity in the direct pathways under parkinsonian state.