光遗传学通道（ChR2）对螺旋神经节细胞兴奋性调控机制的研究

项目名称： 光遗传学通道（ChR2）对螺旋神经节细胞兴奋性调控机制的研究

项目编号： No.81470700

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： 于宁

作者单位： 中国人民解放军总医院

项目金额： 73万元

中文摘要： 耳聋严重影响人们的生活。目前重度、极重度耳聋有效治疗手段是植入人工耳蜗，直接刺激听神经形成人工听觉。但人工耳蜗价格高昂，给患者及社会带来巨大经济负担，亟需寻找成本低廉、长效的替代方法。光遗传学通道（ChR2）被广泛应用于脑细胞的神经活动研究。目前ChR2通道在耳蜗螺旋神经节细胞中的表达及功能调控等方面仍缺乏直接实验依据。本研究拟将光敏感通道蛋白（ChR2）基因通过多种载体导入内耳残存螺旋神经节细胞，利用光敏感蛋白具有的光电换能特性，实现音频能量向神经电信号的转换，并通过听觉传导通路将冲动传至听觉皮层从而产生听觉。以光遗传学通道（ChR2）对螺旋神经节细胞兴奋性调控机制的研究入手，可以为耳聋的发生机制及临床治疗提供新理论依据和思路，对提高国民健康水平、改善耳聋人群的生活质量具有重要意义。

中文关键词： 聋病；耳蜗；螺旋神经节细胞；光遗传学；ChR2通道

英文摘要： Hearing loss is a serious disease that affects people's life. At present, Cochlear implant is an efficient therapeutic way for the heavily or profound hearing loss which would promote the formation of human auditory via stimulating the auditory nerve directly. Due to the high cost of the of cochlear implant which will aggravate the economic burden to patients and society , low cost and long efficiency alternative method need to be found. Optogenetics channel (ChR2) is widely used in the activity of neural cells in the brain. There is still not enough evidence which is proved that ChR2 is expressed and exhibits functions in spiral ganglion cells (SGNs) in the cochlea. Here, we present a novel strategy to transfect the remanent SGNs by ChR2 which is carried by various vectors. Optogenetics channel (ChR2) posses the characteristics of optical-eletrical switch that will promote acoustic signals into the nerve impulses. Finally, the auditory system would transduce the signals to the auditory cortex which account for the formation of mammalian hearing. The exacting regulation mechanism of Optogenetics (ChR2) on SGNs not only paved the way for the underlying mechanism of hearing loss and clinical therapy but also improved the health level and quality of life for people suffering hearing loss.

英文关键词： Deafness;Cochlea;spiral ganglion neuron;optogenetics;Channelrhodopsin-2