水杨酸钠介导的听皮层与海马区之间神经连接的分子机制研究

Tinnitus is a common clinical disorder. The mechanisms of tinnitus are poorly understood and the therapeutic efficacy is unsatisfactory. Tinnitus discomforts people and severe patients suffer anxiety and tendency of suicide. The auditory cortex plays an important role during the development of tinnitus. The limbic system may be a new pathway of tinnitus besides the classical auditory pathway. The limbic system plays an important role in the generation of negative emotions such as anxiety and depression during the process of tinnitus and have influence on the further development of tinnitus. Previous study found synchronous increased excitability between auditory cortex and limbic system during the process of tinnitus, indicate there is some kind of neural connections between the two neural regions, but the exact mechanism is unknown. In this research, based on the classical animal models of tinntus induced by salicylate, in the auditory center (part of auditory cortex) and hippocampus(part of limbic system) we record changes of the single unit firing rate with single-unit activity technology and energy neurotransmitter, ion and other biologically active small molecule substance with in vivo electrochemical analysis methods developed recently in the auditory pathway, and we attempt to reveal the molecular mechanism of neural connections between auditory cortex and hippocampus in the pathogenesis of tinnitus . This research not only will be of great importance in the mechanism but also treatment of tinnitus.

耳鸣是临床中常见问题，其发病机制尚缺乏深入研究并且治疗效果欠佳。耳鸣影响患者的生命质量，严重的耳鸣患者可出现焦虑状态及自杀倾向。听觉中枢是研究耳鸣的经典部位。边缘系统是经典听觉传导通路之外介导耳鸣发生的一个新的途径，在耳鸣患者焦虑抑郁等不良情绪发生过程中起到重要作用，并对耳鸣的进一步发展产生影响。前期研究发现耳鸣发生过程中，听觉中枢和边缘系统兴奋性同步增高，提示两者之间存在某种神经连接，但具体机制不详。本研究在水杨酸钠诱导的经典耳鸣动物模型上，利用单细胞放电技术及新建的活体电化学分析方法，在耳鸣过程中客观监测听觉中枢中听皮层和边缘系统中海马区之间神经电活动，并同时活体动态研究了能量物质、神经递质、离子等多种生物活性小分子物质的变化规律，试图揭示听皮层与海马区之间神经连接的分子机制在耳鸣发病机制中的作用，同时为耳鸣的治疗提供新的药物作用靶点和治疗思路。

耳鸣是临床中常见问题，其发病机制尚缺乏深入研究并且治疗效果欠佳。耳鸣影响患者的生命质量，严重的耳鸣患者可出现焦虑状态及自杀倾向。听觉中枢是研究耳鸣的经典部位。边缘系统是经典听觉传导通路之外介导耳鸣发生的一个新的途径，在耳鸣患者焦虑抑郁等不良情绪发生过程中起到重要作用，并对耳鸣的进一步发展产生影响。前期研究发现耳鸣发生过程中，听觉中枢和边缘系统兴奋性同步增高，提示两者之间存在某种神经连接，但具体机制不详。.本研究在水杨酸钠诱导的经典耳鸣动物模型上，利用单细胞放电技术及新建的活体电化学分析方法，在耳鸣过程中客观监测听觉中枢中听皮层和边缘系统中海马区之间神经电活动，并同时活体动态研究了能量物质、神经递质、离子等多种生物活性小分子物质的变化规律。.本研究重复并验证耳鸣的动物行为学模型；微电极植入大鼠听皮层及海马区核团进行神经元单位放电记录，结果显示正常组与耳鸣组听皮层神经元及海马区神经元放电率存在显著性差异；建立微透析取样方法并测定实验组豚鼠前庭内侧核谷氨酸平均浓度较对照组显著提高，差异有统计学意义；测定了大鼠听觉中枢皮层及海马区核团抗坏血酸的浓度；耳鸣组大鼠听皮层、海马区葡萄糖和乳酸水平显著性升高；水杨酸钠作用后大鼠听皮层及海马区内多巴胺和五羟色胺水平显著性地升高；耳鸣动物模型听皮层及海马区出现镁离子电流响应降低。.本研究试图通过上述研究结果揭示听皮层与海马区之间神经连接的分子机制在耳鸣发病机制中的作用，同时为耳鸣的治疗提供新的药物作用靶点和治疗思路。