帕金森病小鼠模型黑质纹状体通路的形态学改变  

Morphological changes of the nigrostriatal pathway in a mouse model of Parkinson's disease

作　　者：贾妍[1] 徐长磊[1] 徐群渊[1] 

机构地区：[1]首都医科大学北京神经科学研究所,北京市神经再生修复研究重点实验室,教育部神经变性病重点实验室,北京100069

出　　处：《解剖学报》2012年第3期293-298,共6页Acta Anatomica Sinica

基　　金：国家重点基础研究发展计划资助项目(2007CB947704)

摘　　要：目的观察帕金森病小鼠模型黑质纹状体通路随病程进展而发生的形态学变化,从新的视角探讨帕金森病的病理生理机制。方法正常C57小鼠36只,随机分为生理盐水组和1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)组,每组18只,于注射后第7、14、21、25、28、35天取材,利用免疫组织化学、免疫荧光技术和激光扫描共焦显微镜观察黑质多巴胺能神经元的数量、在纹状体内投射的神经纤维密度及其在纹状体直接通路和间接通路神经元(D1R/D2R阳性神经元)上的分布比例。结果注射MPTP后,黑质多巴胺能神经元减少40%～50%;纹状体内多巴胺能神经纤维数量呈现先减少后增加的过程:第21天最少,仅为正常的20%;第35天最高,达到正常的45%;多巴胺能神经纤维在纹状体D1R/D2R阳性神经元上的分布比例也有先低后高的表现:第21天最低,第35天最高,与生理盐水组相比差异有显著性。结论 MPTP帕金森病模型小鼠的黑质纹状体通路呈现多巴胺能神经纤维再生现象,再生的多巴胺能神经纤维更多地分布于其直接通路的神经元上。Objective To observe morphological changes in the nigrostriatal pathway by progress of parkinsonism in a mouse model, in order to investigate the pathophysiology of Parkinson＇ s disease from different contexts and to provide some new clues for Parkinson＇ s prevention, delay, and treatment. Methods Thirty-six C57 mice were randomly divided into the saline control and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine （MPTP） injection groups, with eighteen mice per group. The number of dopaminergic neurons in the substantia nigra, their nerve fiber densities and distributions on the striatal neurons with the direct and indirect pathway cells （dopamine D1 receptors/dopamine D2 receptors positive, D1R/ D2R positive） in the striatum were observed by immunohistochemistry and confocal microscopy at 7, 14, 21, 25, 28 and 35 days after the injection. Results The number of dopaminergic neurons reduced to 40% -50% in the substantia nigra after injection of MPTP. Compared with the control, the decrease of dopaminergic fibers in the striatum showed a tendency that had an early reduction followed by an increase, with a minimum at day 21 （loss of 20% fibers） , and reaching 45% fibers at the 35th day after injection. The distribution ratio of the dopaminergic terminals on striatal neurons to D1R/D2R positive cells was relatively low at day 21, and reached a peak on the day 35. Conclusion The dopaminergic fibers in the striatum show a significant regeneration after a MPTP lesion of the substantia nigra, and these regenerated fibers distribute mostly on those neurons in the direct pathway. The balance of dopamine＇ s activity regulation on the direct and indirect pathways of basal ganglia is broken. This may be an important feature of pathophysiology of Parkinson＇ s disease.

关 键 词：帕金森病 多巴胺能神经元 神经纤维 多巴胺受体 免疫组织化学 免疫荧光 小鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]