实时钙成像研究脑深部电刺激治疗帕金森病的机制

项目名称： 实时钙成像研究脑深部电刺激治疗帕金森病的机制

项目编号： No.81471387

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 孙伯民

作者单位： 上海交通大学

项目金额： 70万元

中文摘要： 帕金森病（Parkinson's disease, PD）是最常见的神经退行性疾病之一，严重影响中老年人的身体健康。临床实践表明，脑深部电刺激（DBS）内侧苍白球或丘脑底核有效改善PD患者的运动功能。目前认为是因为调节基底节-运动皮层异常环路。但是DBS如何调节环路中的神经元活动并不明确，原因是DBS本身产生很强的电信号，用传统电极记录到的神经元放电信号因此受到干扰。课题组前期研究发现高频电刺激PD大鼠丘脑底核抑制基底节输出核团钙调蛋白的表达，表明基底节核团兴奋性下降，但由于不是对神经细胞活动的实时观察，结果存在一定局限性。本课题中，我们采用先进的深部钙成像技术，实时观察DBS MTPT致损PD猴内侧苍白球时，内侧苍白球和运动皮层神经元放电水平，同时用ECoG记录运动皮层电位。本研究将揭示DBS治疗PD对运动神经环路中神经元的影响，为DBS治疗PD及其他神经精神疾病提供新思路和新方法。

中文关键词： 脑深部电刺激；基底节-皮层环路；钙成像；帕金森病；神经元放电

英文摘要： Parkinson's disease (PD) is one of the most common neurodegenerative disease, which damages the health of middle aged and elderly people. Deep brain stimulation (DBS) efficiently improve the motor functions of PD patients. Recently, the studies indicated DBS might inhibit the disorder of basal ganglia-cortex network. However, how the stimulated neurons responses during DBS is still not clear. In previous study, we found subthalamic DBS inhibited the expression of calcium-bingding protein Calbindin-28 in basal ganglia output nucleus of 6-OHDA injuried PD rats, which indicates the STN DBS reduces the activity of neurons in the basal ganglia output nucleus. However, it's not the real time observation of neuronal activity during DBS. In this study, the optical calcium imaging system will be implanted into the internal Globus Pallidus of MTPT injuried rhesus to investigate the calcium level and spiking of the neurons when high and low frequency stimulation are given out respectively. Additinally, the ECoG will be used to record the motor cortical potential to study the correlation of the electrical activity of motor cortex and the neuronal spiking of motor cortex. The results of study will uncover the mechanism of DBS concerning the neuron responses inside the basal ganglia- motor cortex network, which will bring out new ideas to the treatment of PD and other neurological and psychiatric diseases.

英文关键词： Deep brain stimulation;Basal ganglia-cortex network;Calcium imaging;Parkinson's disease;Neuronal spiking