發(fā)布時(shí)間：2018-03-19 17:53

  本文選題：膽堿能神經(jīng)元　切入點(diǎn)：放射狀膠質(zhì)細(xì)胞　出處：《吉林大學(xué)》2009年博士論文　論文類型：學(xué)位論文

【摘要】： 研究端腦發(fā)育膽堿能神經(jīng)元發(fā)生的機(jī)制是理解中樞神經(jīng)系統(tǒng)功能,尋找中樞神經(jīng)系統(tǒng)疾病治療新靶點(diǎn)的基礎(chǔ),也是探索干細(xì)胞定向分化、細(xì)胞移植治療和組織工程修復(fù)損傷不可缺少的步驟。本實(shí)驗(yàn)從研究膽堿能神經(jīng)元的胚胎來源入手,逐步深入探索其獲得膽堿能表型特征的細(xì)胞和分子機(jī)制。首先,使用流式細(xì)胞術(shù)確定了胚胎大鼠端腦膽堿能神經(jīng)元發(fā)生的時(shí)間;采用形態(tài)學(xué)和體外細(xì)胞培養(yǎng)技術(shù)證實(shí)了大腦皮層和基底神經(jīng)節(jié)膽堿能神經(jīng)元分別來源于端腦背側(cè)和腹側(cè)放射狀膠質(zhì)細(xì)胞群;實(shí)驗(yàn)結(jié)果還證實(shí)第三腦室室管膜細(xì)胞產(chǎn)生膽堿能前體細(xì)胞,可能形成基底前腦神經(jīng)核團(tuán)的Ch5,Ch6膽堿能神經(jīng)細(xì)胞群。其次,通過骨形態(tài)發(fā)生蛋白-4對膽堿能神經(jīng)元的誘導(dǎo)作用,證實(shí)了在端腦細(xì)胞培養(yǎng)體系中不同濃度BMP4對膽堿能神經(jīng)元發(fā)生數(shù)量有不同影響,并且利用這一特點(diǎn),通過改變培養(yǎng)體系中骨形態(tài)發(fā)生蛋白-4濃度,采用RT-PCR技術(shù)找出mRAN表達(dá)隨之發(fā)生變化的同源域轉(zhuǎn)錄因子Isl-1。實(shí)驗(yàn)結(jié)果提示,膽堿能神經(jīng)元發(fā)生是在一定濃度骨形態(tài)發(fā)生蛋白-4誘導(dǎo)下神經(jīng)祖細(xì)胞表達(dá)LIM同源域轉(zhuǎn)錄因子Isl-1,并與膽堿能基因座啟動(dòng)子的特定位點(diǎn)結(jié)合,啟動(dòng)膽堿能基因座轉(zhuǎn)錄的結(jié)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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2009
【分類號(hào)】：R329.1

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本文編號(hào)：1635361