骨形态发生蛋白4对胆碱能神经元发生关键转录因子表达的调节

发布时间：2018-02-24 09:21

本文关键词： 端脑发育胆碱能神经元骨发生形态蛋白-4 胰岛素基因1增强子蛋白　出处：《吉林大学》2010年硕士论文　论文类型：学位论文

【摘要】： 由于基底前脑胆碱能神经元参与人类运动,学习和记忆,又是临床上多种中枢神经系统退行性疾病的靶细胞,因此,研究诱导胆碱能发生的关键细胞外信息分子和控制胆碱能基因座转录的同源域蛋白对于揭示胆碱能神经元的发生不仅具有重要的理论意义,而且还有巨大的应用价值。本课题组在前期工作中发现,在E14大鼠端脑细胞体外培养体系中,20ng／ml BMP4可增加乙酰胆碱转移酶(ChAT)免疫反应阳性细胞数,40ng／ml BMP4可减少ChAT阳性细胞数量。此结果表明不同浓度BMP4对胆碱能神经元发生和分化具有不同影响。为进一步证实在端脑体外培养体系中不同浓度BMP4对同源域蛋白ISL-1表达是否与ChAT的表达相一致,以推断胆碱能神经元发生是否通过BMP4信号传导途径作用于同源域蛋白ISL-1而起作用。本实验采用免疫细胞化学和定量分析技术,检测了不同浓度BMP4诱导ISL-1蛋白的表达,其结果显示,实验各组均可见同源域蛋白ISL-1在细胞核中表达。其中10ng／ml BMP4组ISL-1免疫反应阳性细胞数与对照组相比无显著性差异；20ng／ml BMP4组ISL-1阳性细胞数与其它组相比明显增加,此作用可被BMP抑制剂Noggin阻断；40ng／ml BMP4组ISL-1阳性细胞数显著减少。此结果不仅与前期工作中不同浓度BMP4对ChAT阳性细胞数量的影响相一致,而且与不同浓度BMP4诱导ISL-1mRNA表达的结果相吻合。说明BMP4信号传导途径不但参与了胆碱能神经元发生过程,同时可诱导同源域蛋白ISL-1表达。此结果还提示BMP4细胞外信息分子可能通过诱导同源域ISL-1蛋白来调控端脑神经祖细胞向胆碱能神经元分化。
[Abstract]:Because basal forebrain cholinergic neurons are involved in human movement, learning and memory, they are also the target cells for many degenerative diseases of the central nervous system. The study of key extracellular pheromones and homologous proteins that control the transcription of cholinergic loci are not only of theoretical significance in revealing the occurrence of cholinergic neurons, but also in the pathogenesis of cholinergic neurons. Moreover, there is great application value. In our earlier work, we found that, In E14 rat terminal brain cells cultured in vitro, 20ng / ml BMP4 increased the number of acetylcholine transferase (BMP4) immunoreactive cells and 40ng / ml BMP4 decreased the number of ChAT positive cells. In order to further confirm whether the ISL-1 expression of homologous domain protein ISL-1 is consistent with that of ChAT in the culture system of endencephalon in vitro with different concentrations of BMP4. In order to infer whether cholinergic neuronogenesis acts on homologous domain protein ISL-1 through BMP4 signal transduction pathway, the expression of ISL-1 protein induced by different concentrations of BMP4 was detected by immunocytochemistry and quantitative analysis. The results showed that homologous domain protein ISL-1 was expressed in the nucleus of all groups, and the number of ISL-1 immunoreactive cells in 10ng / ml BMP4 group was not significantly different from that in control group. The number of ISL-1 positive cells in 20ng / ml BMP4 group was significantly higher than that in other groups. The number of ISL-1 positive cells in 40 ng / ml BMP4 group blocked by BMP inhibitor Noggin was significantly decreased. The results were not only consistent with the effect of different concentrations of BMP4 on the number of ChAT positive cells in the previous work. These results are consistent with the results of ISL-1mRNA expression induced by different concentrations of BMP4, indicating that BMP4 signaling pathway is not only involved in the process of cholinergic neuronal development, but also in the process of cholinergic neurons. The expression of homologous domain protein ISL-1 was also induced, which suggested that the extracellular signaling molecules of BMP4 might regulate the differentiation of terminal neural progenitor cells into cholinergic neurons by inducing homologous domain ISL-1 protein.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R329.1

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