SURVIVAL AND DEATH OF NEURONS

神经元的生存和死亡

• 批准号: 3396920
• 负责人: Timothy J Timothy J Cunningham Cunningham
• 金额: $ 17.65万
• 依托单位: ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-07-01 至 1990-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3396920
• 关键词: afferent nerve; autoradiography; cell death; central nervous system; congenital brain disorder; dialysis; electron microscopy; gel electrophoresis; high performance liquid chromatography; histochemistry /cytochemistry; innervation; laboratory rat; nervous system regeneration; nervous system transplantation; neural degeneration; neurogenesis; neurons; newborn animals; retinal ganglion; synapses; tissue /cell preparation; visual pathways

The experiments outlined in this proposal focus on the requirements of neurons in the CNS for survival and normal functioning, both during development and following brain injury in adults. One general hypothesis to be tested is that the trophic requirements of developing and mature neurons are similiar. We will continue our investigations of the nature and specificity of trophic interactions in the visual system of developing rats, using both explant culture and intracranial transplantation methods, and begin the search for the specific molecules that underly these interactions. Included in these experiments is a test of the possibility that the same trophic agents are produced in different regions of the developing neocortex, but the timing of their production differs so that the survival of specific subcortical neurons is supported at the appropriate time. We will also follow up on recent results showing a survival-promoting effect of neocortical transplants in adult rats by testing the specificity and mechanisms of this effect (including a test for the operation of the same specific trophic molecules that support developing neurons). Another general hypothesis to be tested relates to a neuron's requirement for a particular pattern of synaptic connections, one in which afferent and target contacts are balanced to fulfill an intrinsic requirement for normal functioning. We propose that cells make adjustments in their connectivity during development in order to achieve this balance. Preliminary studies on locus coeruleus neurons of mutant mouse tottering and retinal ganglion cells of rats monocularly enucleated at birth are consistent with the occurrence of such synaptic adjustments; these results will be confirmed and extended in order to test this hypothesis more directly.

本提案中概述的实验重点是 中枢神经系统中神经元生存和正常的要求 在发育期间和在脑损伤之后的功能 成年人。 要检验的一个一般假设是营养 发育和成熟神经元的要求相似。 我们 将继续我们调查的性质和特异性 使用的大鼠视觉系统中的营养相互作用 外植体培养和颅内移植方法，以及 开始搜索这些基础的特定分子 互动。 这些实验中包括 同一营养剂在不同的可能性 发展中新皮层的地区，但他们的时机 生产有所不同，因此特异性下皮质的存活率 在适当的时间支持神经元。 我们还将跟随 最新结果显示了生存的促进作用 通过测试特异性和 这种效果的机制（包括对操作的测试 支持发展的相同特定的营养分子 神经元）。 要测试的另一个一般假设与 神经元对特定突触模式的要求 连接，一个传递和目标联系人的连接 平衡以满足正常的内在要求 功能。 我们建议细胞对其进行调整 开发过程中的连通性是为了实现这一平衡。 关于突变小鼠的基因座神经元的初步研究 大鼠的颤动和视网膜神经节细胞是单眼的 出生时与这种突触的发生是一致的 调整；这些结果将被确认并扩展为顺序 更直接地检验该假设。