Motoneurons deprived of trophic support in vitro require new gene expression to undergo programmed cell death.
Motoneurons deprived of trophic support in vitro require new gene expression to undergo programmed cell death.
复制标题
体外失去营养支持的运动神经元需要新的基因表达来经历程序性细胞死亡。
DOI：
10.1002/neu.480250809
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Schwartz,LM
中科院分区：
文献类型：
--
作者：
Milligan,CE;Oppenheim,RW;Schwartz,LM
在正常发育过程中，大量神经元通过程序性细胞死亡而死亡。这种现象已在鸡胚的侧向运动柱中得到广泛研究，其中最初产生的运动神经元中约有50%随后死亡，部分原因是竞争有限的靶源性营养支持。RNA和蛋白质合成的抑制剂在体内阻断这种细胞损失，表明需要新的基因表达（Oppenheim等人，1990年）。在鸡脊髓运动神经元死亡之前，可以从其脊髓中分离出相对纯的运动神经元群体用于体外研究。接种肌肉提取物（靶源性营养支持的有效来源）的细胞存活，并具有大的、相亮的细胞体和广泛的神经突生长。相反，在没有肌肉提取物的情况下培养的运动神经元在48小时内死亡。这种死亡可以被RNA合成抑制剂放线菌素D阻断，当细胞变得致力于死亡时，这表明新的基因表达是细胞死亡所必需的。DNA断裂和核浓缩表明这些细胞中的一些通过凋亡而死亡。因此，似乎在体内观察到的运动神经元发育的许多方面可以在体外重建。这些文化可以被用来作为一个模型系统，用于研究神经元死亡，并可能有助于了解的分子机制，介导的程序性细胞死亡在神经元发育。John Wiley & Sons，Inc.
During normal development, large numbers of neurons die by programmed cell death. This phenomena has been extensively studied in the lateral motor column of chick embryos, where approximately 50% of the motoneurons that are initially produced, subsequently die due in part to competition for a limited supply of target-derived trophic support. Inhibitors of RNA and protein synthesis block this cell loss in vivo, indicating a requirement for new gene expression (Oppenheim et al., 1990). Prior to their commitment to death, motoneurons can be isolated as a relatively pure population from chick spinal cord for in vitro study. Cells plated with muscle extract, a potent source of target-derived trophic support, survive, and have large, phase-bright cell bodies and extensive neurite outgrowth. In contrast, motoneurons cultured in the absence of muscle extract die within 48 h. This death can be blocked by the RNA synthesis inhibitor actinomycin D, at the time when the cells become committed to die, suggesting that new gene expression is required for cell death. DNA fragmentation and nuclear condensation indicate that some of these cells die by apoptosis. Therefore, it appears that many aspects of motoneuron development observed in vivo can be reconstituted in vitro. These cultures can be used as a model system for studying neuronal death and may contribute to an understanding of the molecular mechanisms that mediate programmed cell death during neuronal development. 1994 John Wiley & Sons, Inc.