经颅磁刺激对帕金森病运动功能及突触可塑性的影响及机制研究

Parkinson's disease（PD）is a common neurodegenerative disorder with no clinically efficient remedy available at the moment. Many studies have confirmed that transcranial magnetic stimulation (TMS) can improve movement disorders of PD. However, its application in clinical practice is limited due to the mechanism is unclear. Synaptic plasticity plays a important role in nerve injury and repair. In PD, there is a pathological synaptic plasticity and modulation of cortico-striatal synaptic plasticity might prove useful in the treatment of motor symptoms. In this project the effect of high-frequency and low-frequency transcranial magnetic stimulation on the motor function of Parkinson's disease model are studied. Synapse number、synapse ultrastructure and synaptogenesis are detected by electron microscopy、confocal laser scanning microscopy、immunofluorescence、Western blot. The relationship between N-methyl-D-aspartate (NMDA) receptor signaling complex and transcranial magnetic stimulation is also studied. Meanwhile, we also investigate the role of NMDAR antagonist in order to explain the mechanism. Our study will provide a theoretical basis for the clinical applications of the transcranial magnetic stimulation.

帕金森病(Parkinson's disease, PD)是最常见的慢性神经变性性疾病之一，目前临床尚无有效的治疗方法。已有很多研究证实经颅磁刺激能改善PD的运动障碍，然而由于机制不清限制了其在临床中的应用。突触可塑性是神经损伤和修复的神经生物学基础，在PD恢复中扮演重要角色。本项目拟分别采用高频和低频经颅磁刺激观察经颅磁刺激对帕金森病大鼠运动功能的改善作用，利用电镜、激光共聚焦显微镜、免疫荧光、western blot等技术研究经颅磁刺激后纹状体突触数、突触超微结构改变以及神经元树突生长和突触发生的变化，并分析相关突触蛋白表达，同时利用特异性拮抗剂干预，分析经颅磁刺激影响突触可塑性的分子机制，为推动经颅磁刺激在临床的应用提供理论基础。

本项目利用动物模型、细胞模型、组织学、分子生物学及磁场操控技术，就经颅磁刺激对突触可塑性的影响及可能的作用机制开展相关研究。从整体动物水平、细胞水平和分子水平上研究了经颅磁刺激与突触可塑性相关分子的相互关系和分子机制。研究结果表明，经颅磁刺激对突触可塑性的调节具有时间差效应，可增强突触素的表达，这一作用与突触后膜上NMDA受体信号复合物有关。尤其是NMDA受体和CaMK II，它们的激活在突触可塑性中起重要作用，直接影响到突触信号的传递和突触的重建。电镜等组织学显示，经颅磁刺激后，脑区突触数量增多，突触相关结构性可塑指标有明显改善。通过研究，经颅磁刺激可调节突触可塑性得到进一步证实，对经颅磁刺激治疗某些疾病的机制有了更深入的认识；上述结果为经颅磁刺激在临床的应用提供理论基础，对于推动经颅磁刺激在医学中的应用具有重大意义。