电休克刺激对SD大鼠脑中枢神经系统可塑性的影响

Electroconvulsive therapy（ECT）that has affirmative effects on mental disorder can remit rapidly a variety of syndrom of mental disorder. But it is always in empirial application stage because of the unclear mechanism. In present study, male SD rats will be made as subjects, and they will be divided into three groups:single electroconvulsive seizure(ECS) group, chronic ECS group and sham ECS group. Electroconvulsive seizure will be generated by an ECS apparatus for animal (57800ECT unit; UGO BASILE, Italy). Brain slices and patch clamp recording techniques will be used to detect the physiological characteristics of the prefrontal, hippocampus, nucleus accumbens in three groups. Physiological characteristics includs brain network oscillations,excitatory postsynaptic potential(EPSP), inhibitory post postsynaptic potential(IPSP); transmission electron microscope will be used to observe the structural plasticity of the above encephalic region. structural plasticity includs organelle morphology, vesicle morphology and number,and synaptic structure；Gene expression profile microarray will be used to screen mRNA differentially expressed genes in brain regions that correspond to the regions in the research of physiological characteristics. We will pay our attention to the differentially expressed genes which is related to the physiological characteristics and the structural plasticity acorrding to the clue provided by performing programe of functional enrichment analysis, and will selecte these genes in further research which is to analyze the local in the brain by using in situ hybridization in the future. By doing so,to get the information about the effects of ECS on functional and structrue plasticity. The present study not only is advantage to exploring the mechanism of ECT but also provide with theoretical basis for applying ECT in clinic scientifically. It is most important that will provide with new clues for the research on mental illness pathological mechanism.

电休克治疗(ECT)是精神科普遍应用、疗效肯定的治疗方法，可快速缓解多种症状，但其治疗机制不清，临床应用缺乏理论依据。本研究以雄性SD大鼠为研究对象，应用动物电休克刺激仪制备单次电刺激、慢性电刺激与伪刺激模型，应用脑片与脑片膜片钳技术检测不同组别大鼠脑额叶、海马、伏膈核区神经元电生理特征(脑神经网络振荡、兴奋性和抑制性突触后电位)；应用透射电镜技术观察模型上述脑区神经元结构可塑性(细胞器、囊泡形态和数量、突触结构等)变化；应用基因表达谱芯片筛选不同组别大鼠脑额叶、海马、伏隔核区mRNA的差异表达，进一步确定功能上与神经电生理活性及结构可塑性相关联的差异表达基因；根据功能多模态富集分析线索，获得拟通过原位杂交进行相关基因的脑区定位表达分析的信息。本研究预期结果将初步明确电休克剌激对鼠脑神经功能与结构可塑性的影响，探讨ECT的治疗机制，为ECT的临床应用提供理论依据，也将为精神疾病病理机制研究提供新线索。

电休克治疗(ECT)是精神科普遍应用、疗效肯定的治疗方法，可快速缓解多种症状，但其治疗机制不清，临床应用缺乏理论依据。本研究应用动物电休克刺激仪制备单次电刺激、慢性电刺激与伪刺激模型，应用脑片与脑片膜片钳技术检测不同组别鼠脑额叶、海马、伏膈核区神经元电生理特征(脑神经网络振荡、兴奋性和抑制性突触后电位)；应用透射电镜技术观察模型上述脑区神经元结构可塑性(细胞器、囊泡形态和数量、突触结构等)变化；应用基因表达谱芯片筛选不同组别鼠脑额叶、海马、伏隔核区mRNA的差异表达，进一步确定功能上与神经电生理活性及结构可塑性相关联的差异表达基因。结果发现，ECS可以引起基因差异表达，值得关注的基因有位于代谢通路上的差异高表达基因和低表达的MAPK信号通路、谷氨酸能信号通路、膜蛋白结合区及钙离子信号通路上的差异表达基因；ECS可以导致动物脑神经元自发活动增强，但对刺激反应产生LTP效能减弱；可抑制氯胺酮所致的r-超同步现象；ECS可以改善酮腙所致的中枢神经脱髓鞘改变，促进神经髓鞘形成重要标志物MBP、CNPase蛋白的表达，修复脑白质损伤。得出以下结论：ECS可能通过快效应途径与慢效应途径两种途径改善精神症状，快效应途径通过电刺激调整神经元电生理活性，进一步影响神经生物学功能（基因转录、递质释放等），同时在这些功能基础上，修复神经元功能，调整神经功能网络，改善精神症状成为慢效应途径。本研究将为电休克治疗机制提供实验室证据，为ECT的临床应用提供理论依据，也将为精神疾病病理机制研究提供新线索。