Neurotrophic interactions in the development of spinal cord motoneurons.
Neurotrophic interactions in the development of spinal cord motoneurons.
复制标题
脊髓运动神经元发育中的神经营养相互作用。
DOI：
10.1002/9780470513675.ch10
复制
发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Haverkamp,LJ
中科院分区：
文献类型：
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作者：
Oppenheim,RW;Haverkamp,LJ
脊髓运动神经元的最终数量是通过两步过程获得的，包括前体细胞的增殖和有丝分裂后神经元部分（约50%）的细胞死亡损失。尽管运动神经元的定型数量的增殖机制尚不清楚，但来自体外和体内研究的大量证据表明，获得群体大小的第二步（细胞死亡）是由运动神经元与其传出靶点和传入输入的相互作用控制的。运动神经元存活的靶向影响被认为是由肌肉活动和来自横纹肌的有限数量的神经营养因子的竞争来调节的。然而，证据表明，这种假定的神经营养因子实际上调节运动神经元存活在vivo一直缺乏。利用胚胎后肢（第8-9天）的粗提物和部分纯化的提取物，我们发现在正常细胞死亡期（第5-10天）用这些试剂处理鸡胚卵，可挽救大量运动神经元免于变性。肾或肺提取物和热灭活后肢提取物无效。部分纯化提取物的存活诱导活性具有剂量依赖性和发育调节性。感觉，交感神经和胆碱能交感神经节前神经元的人口的生存与后肢提取物的治疗不受影响。早期目标（后肢）去除后发生的大量运动神经元死亡通过每日用后肢提取物治疗而部分改善。胰蛋白酶处理后，提取物的存活诱导活性丧失。总之，这些结果表明靶源性蛋白或多肽神经营养因子参与体内运动神经元存活的调节。
The final number of spinal cord motoneurons is attained by a two‐step process involving the proliferation of precursor cells and the loss by cell death of a proportion (≈50%) of the post‐mitotic neurons. Although the mechanisms responsible for the proliferation of stereotyped numbers of motoneurons are not understood, considerable evidence fromin vitroas well asin vivostudies indicates that the second step in attaining population size (cell death) is control‐led by the interaction of motoneurons with both their efferent targets and their afferent inputs. Target influences on motoneuron survival are thought to be regulated by muscular activity and by competition for limited amounts of neurotrophic factors derived from striated skeletal muscles. However, evidence that such putative neurotrophic factors actually modulate motoneuron survivalin vivohas been lacking. Using crude and partially purified extracts from embryonic hindlimbs (Days 8–9) we have found that the treatment of chick embryosin ovowith these agents during the normal cell death period (Days 5–10) rescues a significant number of motoneurons from degeneration. Kidney or lung extracts and heat‐inactivated hindlimb extracts were ineffective. The survival‐inducing activity of partially purified extract was dose dependent and developmentally regulated. The survival of sensory, sympathetic and a population of cholinergic sympathetic preganglionic neurons was unaffected by treatment with hindlimb extract. The massive motoneuron death that occurs after early target (hindlimb) removal was partially ameliorated by daily treatment with the hindlimb extract. Survival‐inducing activity of the extract is lost after trypsin treatment. Taken collectively these results indicate that a target‐derived protein or polypeptide neurotrophic factor is involved in the regulation of motoneuron survivalin vivo.