听皮层GABAB受体在耳鸣产生机制中的作用

项目名称： 听皮层GABAB受体在耳鸣产生机制中的作用

项目编号： No.81200741

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 罗彬

作者单位： 安徽医科大学

项目金额： 23万元

中文摘要： 耳鸣的发病率很高，但目前临床上缺乏有效治疗手段。已有研究显示，听觉中枢兴奋性增强或抑制性减弱，导致听觉中枢超兴奋，可能是耳鸣产生的原因，但耳鸣产生的结构基础仍不清楚。用于增强抑制性系统的药物，如GABAB受体激动剂baclofen，被动物实验研究证明可以抑制耳鸣。申请人前期研究结果证明，baclofen对听觉丘脑兴奋性突触传递的压抑要明显强于对抑制性突触传递的压抑，提示baclofen可降低兴奋性，因此我们推测，听觉中枢GABAB受体的下调可能是耳鸣产生的结构基础之一，而baclofen正是通过增强GABAB受体的功能，使兴奋抑制再次恢复平衡，从而起到治疗耳鸣的作用。本课题拟通过脑片和单细胞膜片钳技术，结合形态学等方法，利用噪声暴露制作大鼠耳鸣模型，研究在耳鸣发生时听皮层GABAB受体是否发生下调，并阐述其潜在的作用机制。这将为耳鸣治疗提供新的靶点，为阐明耳鸣产生的神经机制提供新的方向。

中文关键词： 耳聋；耳鸣；噪声；听皮层；抑制性神经元

英文摘要： In spite of the high incidence of tinnitus, there are no effective treatment for tinnitus. In recent years, most researchers hold the opinion that the neural basis of tinnitus is the imbalance of inhibition and excitation which caused hyperexcitability in the central auditory system and eventually tinnitus occurs, but the underlying structure is not clear. The drugs which can enhance the inhibitory system such as baclofen, the agonist of GABAB receptors are demonstrated to be effective in depressing tinnitus in animal experiment. In our previous study, we found that baclofen depressed excitatory more than inhibitory neurotransmission, which suggested that baclofen can decrease excitation, so we speculate that the down regulation of GABAB receptors might be the structual basis of tinnitus, and baclofen enhances the function of GABAB receptors, and the balance of inhibition and excitation restored, with tinnitus cured. In the present project, we plan to use the technique of patch clamp and morphological method to investigate whether GABAB receptors in noise induced tinnitus animal models are downregulated and try to make clear the underlying mechnism. This will provide new orientation for tinnitus treatment and a new direction for clarifying the neural mechanism of tinnitus.

英文关键词： Hearing loss；tinnitus；noise；auditory cortex；inhibitory neurons