在端脑发育中胆碱能神经元发生机制的研究

发布时间：2018-03-19 17:53

本文选题：胆碱能神经元　切入点：放射状胶质细胞　出处：《吉林大学》2009年博士论文　论文类型：学位论文

【摘要】： 研究端脑发育胆碱能神经元发生的机制是理解中枢神经系统功能,寻找中枢神经系统疾病治疗新靶点的基础,也是探索干细胞定向分化、细胞移植治疗和组织工程修复损伤不可缺少的步骤。本实验从研究胆碱能神经元的胚胎来源入手,逐步深入探索其获得胆碱能表型特征的细胞和分子机制。首先,使用流式细胞术确定了胚胎大鼠端脑胆碱能神经元发生的时间;采用形态学和体外细胞培养技术证实了大脑皮层和基底神经节胆碱能神经元分别来源于端脑背侧和腹侧放射状胶质细胞群;实验结果还证实第三脑室室管膜细胞产生胆碱能前体细胞,可能形成基底前脑神经核团的Ch5,Ch6胆碱能神经细胞群。其次,通过骨形态发生蛋白-4对胆碱能神经元的诱导作用,证实了在端脑细胞培养体系中不同浓度BMP4对胆碱能神经元发生数量有不同影响,并且利用这一特点,通过改变培养体系中骨形态发生蛋白-4浓度,采用RT-PCR技术找出mRAN表达随之发生变化的同源域转录因子Isl-1。实验结果提示,胆碱能神经元发生是在一定浓度骨形态发生蛋白-4诱导下神经祖细胞表达LIM同源域转录因子Isl-1,并与胆碱能基因座启动子的特定位点结合,启动胆碱能基因座转录的结果。
[Abstract]:Studying the mechanism of cholinergic neurons in endencephalic development is the basis of understanding the function of central nervous system and finding new targets for the treatment of central nervous system diseases, as well as exploring the directional differentiation of stem cells. Cell transplantation and tissue engineering are indispensable steps to repair the injury. In this study, we studied the embryonic origin of cholinergic neurons, and gradually explored the cellular and molecular mechanisms for obtaining the phenotypic characteristics of cholinergic neurons. Flow cytometry was used to determine the time of occurrence of cholinergic neurons in the terminal brain of embryonic rats. The cortical and basal ganglia cholinergic neurons originated from the dorsal and ventral radiative glial cell groups of the cerebrum, respectively, were confirmed by morphological and cell culture techniques in vitro. The results also confirmed that the third ventricle ependymal cells produced cholinergic precursor cells, which may form the Ch5 Ch6 cholinergic nerve cell group in the basal anterior brain nucleus. Secondly, the cholinergic neurons were induced by bone morphogenetic protein-4. It was proved that different concentrations of BMP4 had different effects on the number of cholinergic neurons in the endbrain cell culture system, and by changing the concentration of bone morphogenetic protein-4 in the culture system, RT-PCR technique was used to find out the homologous domain transcription factor Isl-1which changed with the expression of mRAN. Cholinergic neuronogenesis is the result of the expression of LIM homologous domain transcription factor Isl-1 in neural progenitor cells induced by bone morphogenetic protein-4, and the activation of cholinergic locus transcription by binding to a specific site of cholinergic locus promoter.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2009
【分类号】：R329.1

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