SURVIVAL AND DEATH OF NEURONS

神经元的生存和死亡

• 批准号: 3396917
• 负责人: Timothy J Timothy J Cunningham Cunningham
• 金额: $ 12.27万
• 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 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3396917
• 关键词: afferent nerve; cell death; central nervous system; congenital brain disorder; electron microscopy; histochemistry /cytochemistry; innervation; nervous system regeneration; nervous system transplantation; neural degeneration; neurons; newborn animals; retinal ganglion; synapses; tissue /cell preparation

The proposed research will test the hypothesis that survival of developing neurons in the central nervous system depends on: 1) access to trophic substances contained within connecting neuronal populations; and 2) the appropriate balance of synaptic connections among these populations. An in vivo assay system, combining neural transplantation and tissue culture techniques, has been developed to test for the existence of target derived trophic factors which promote neuron survival in the developing rat visual system. Posterior cortical tissue from fetal rats is transplanted into infant rats with cortical lesions in order to rescue temporarily thalamic neurons which would normally die rapidly after the lesions. Strategies are proposed to enhance and prolong this neuron rescue, and to identify the most potent sources of trophic support. Other experiments will test the specificity of the trophic influences and whether the effect is mediated by diffusable or transported substances derived from transplanted neurons. It is suggested that once a neuron has achieved this initial trophic support, it must gain an appropriate numerical balance of afferent and target contacts. Quantitative electron microscopic methods will be applied to retinal ganglion cells in experimental situations where this balance is upset. Th experiments will show whether these neurons adjust their connectivity to restore the balance. Both developing and regenerating cell populations will be tested, to determine if adult regenerating neurons retain this requirement for balanced connections. An understanding of the specific requirements of CNS neurons for survival is essential for developing therapies to maintain or restore neuronal populations in conditions of abnormal brain development.

拟议的研究将检验以下假设 中枢神经系统中的神经元取决于：1）获取营养 连接神经元种群中包含的物质； 2） 这些人群之间突触连接的适当平衡。 一个 体内测定系统，结合神经移植和组织培养 已经开发了技术来测试目标的存在 在发育中的大鼠视觉中促进神经元存活的营养因子 系统。 将胎儿大鼠的后皮质组织移植到 带皮质病变的婴儿大鼠，以营救暂时的丘脑 病变后通常会迅速死亡的神经元。 策略是 提议增强和延长这种神经元的救援，并确定 最有效的营养支持来源。 其他实验将测试 营养影响的特异性以及效果是否由 衍生自移植神经元的可扩散或转运物质。 建议一旦神经元达到了最初的营养 支持，它必须获得传入的适当数值平衡和 目标触点。 定量电子显微镜方法将应用 在这种平衡为实验情况下的视网膜神经节细胞 沮丧的。 实验将显示这些神经元是否调整它们的 连接以恢复余额。 开发和再生细胞 将测试种群，以确定成人再生神经元是否 保留对平衡连接的要求。 对 CNS神经元生存的特定要求对于 开发疗法以维持或恢复神经元种群 脑发育异常的条件。