递质剥夺诱导纹状体神经环路及其突触损害机制的实验证实

项目名称： 递质剥夺诱导纹状体神经环路及其突触损害机制的实验证实

项目编号： No.81471288

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： 雷万龙

作者单位： 中山大学

项目金额： 70万元

中文摘要： 纹状体神经环路及突触连接是行使感觉运动、学习记忆、情感认知机能的形态基础，同时也密切牵涉到神经退变性疾病的病理机制。为此，本项目借助神经递质剥夺模型，以及多种形态和分子生物学技术证实；①正常皮质、丘脑、中脑突触输入分别与纹状体不同类型神经元之间突触连接，以及纹状体不同类型神经元相互之间突触连接特征；②递质剥夺对实验动物行为学及纹状体神经元代谢机能的影响；对纹状体神经环路及其突触结构的影响；包括不同来源的突触前和不同性质的突触后成分的形态、数量、突触密度和连接位点，相应蛋白表达水平；对纹状体DA和Glut突触信号通路上相关成分的蛋白和基因表达水平的影响；致使纹状体神经元凋亡及分子机制。此研究旨在补充和完善纹状体环路及突触连接的形态学框架，以及证实递质剥夺对纹状体环路及突触结构的损害机制。此实验资料对于认识和理解纹状体神经环路及突触连接的形态结构、生理机能、以及神经退变病理机制具有重要意义。

中文关键词： 神经退行性疾病；帕金森氏病；发病机制；突触可塑性；多巴胺能神经元

英文摘要： The striatal circuits and synapses are morphologic basis in sensorimotor, learning and mnemonic as well as cognitive functions, which are critically involved in the pathomechanism of neuron degeneration. Threfore, this research project utilizes the model of neurotransmitter deprivation, and the morphological and molecular biological techniques to examine; 1. Morphological characteristics of synaptic connection for cortical, thalamic, mesocephalic inputs targeting striatal different neuron types, and the synaptic connected relation among striatal different neuron types; 2.The alterations for animal behavioristics and striatal energy metabolism induced by neurotransmitter deprivation, and striatal circuit and synaptic structure, including morphology, number, density, connective locus of pre-synaptic and post-synaptic elements, and the expression level for related protein induced by neurotransmitter deprivation; Changes of protein and gene expression level for striatal DA and Glut neurotransmission pathways; Striatal neuron apoptosis and its molecular mechanism induced by neurotransmitter deprivation. The present project aimed to further replenish and perfect morphological frame and synaptic connection of striatal circuit, and definitely confirmed striatal circuit and synapse disruption induced by neurotransmitter deprivation. These morphological data are valuable in fully understanding the morphological structures and the physiological functions, and the nerve degenerative disease's pathomechanism of striatal circuit and synaptic connection.

英文关键词： degenerative disease;Parkinson's Disease;pathomechanism;synaptic plasticity;dopaminergic neuron