中缝核-内嗅皮层5羟色胺能通路在颞叶癫痫发生机制中的作用

项目名称： 中缝核-内嗅皮层5羟色胺能通路在颞叶癫痫发生机制中的作用

项目编号： No.81471316

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： 郭谊

作者单位： 浙江大学

项目金额： 60万元

中文摘要： 脑内5羟色胺（5-HT）能系统在颞叶癫痫发生机制中的作用不明。课题组前期研究发现在早期癫痫形成网络中内嗅皮层可能参与了颞叶癫痫的发生。本课题将采用杏仁核电点燃癫痫模型、光遗传学技术、多通道微电极记录、电生理、免疫组化、免疫印迹方法、PCR等多种技术,验证激活中缝核－内嗅皮层5-HT能通路抑制颞叶癫痫的发生以及对空间记忆和抑郁的作用，明确其作用是通过5-HT1A、5-HT2A和5-HT3受体完成，并观察通路激活和抑制后对中缝核、内嗅皮层和海马的5-HT浓度、5-HT1A受体及5羟色胺转运体mRNA的影响，了解通路激活和抑制后对内嗅皮层和海马各区神经元放电的影响。本研究的完成将有助于我们进一步明确5-HT能系统在颞叶癫痫的发生机制中的具体作用，为今后临床颞叶癫痫患者的抗抑郁治疗提供科学依据。

中文关键词： 颞叶癫痫；5羟色胺；癫痫发生；内嗅皮层；光遗传学

英文摘要： The effect of serotonergic system on the epileptogenesis of temporal lobe epilepsy remains unknow. Our previous studies indicated that the entorhinal cortex may be involved in the epileptogenesis during the early epileptic network. The aim of this project is to validate that the activated raphe nucleus-entorhinal cortex serotonergic pathway can inhibit epileptogenesis and the impairment of memory and depression by using amygdala-kindling model, optogenetics, multichannel microelectrode recording, electrophysiology, immunohistochemistry, western bolt and PCR. To confirm that the function of pathway depends on the 5-HT1A,5-HT2A and 5-HT3 receptors. To investigate that the effects of activation and inhibition of serotonergic pathway on 5-HT concentration, the expression of 5-HT1A receptor and 5-HTT mRNA in raphe nucleus, entorhinal cortex and hippocampus. To clarify the influence of neuron discharge in entorhinal cortex and hippocampus by the activation and inhibition of pathway. Completion of this project will help us to further clarify the role of 5-HT system in the epileptogenesis of temporal lobe epilepsy, it also to provide a scientific basis for antidepressant therap in patients with temporal lobe epilepsy in the future.

英文关键词： temporal lobe epilepsy;serotonin;epileptogenesis;entorhinal cortex;optogenetics