SURVIVAL AND DEATH OF NEURONS

神经元的生存和死亡

• 批准号: 3396922
• 负责人: Timothy J Timothy J Cunningham Cunningham
• 金额: $ 22.07万
• 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 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3396922
• 关键词: autoradiography; axon; axon reaction; cell death; cell differentiation; cell population study; central nervous system; diencephalon; gel electrophoresis; high performance liquid chromatography; immunocytochemistry; laboratory rat; lateral geniculate body; mature animal; monoclonal antibody; nervous system transplantation; neural degeneration; neurogenesis; neurons; newborn animals; protein sequence; visual cortex

Our laboratory has identified a neurotrophic factor active in the geniculocortical pathway of rats in vivo, and the studies described in this proposal will utilize this factor to test directly the validity of the trophic factor hypothesis in the CNS. In particular we will test the idea that a target-derived molecule is important for the survival and differentiation of developing neurons of the dorsal lateral geniculate nucleus (dLGN), as well as the survival of these same neurons after they mature. In addition, an intensive effort is proposed to scale up production of this factor (which is already close to purification) for amino acid sequencing and monoclonal antibody production. This factor is retrieved in vitro from co-cultures of embryonic rat cortex and diencephalon; an important finding concerning its role in vivo is that it is maximally effective in supporting the survival of different sub- population of developing dLGN neurons - separated from their targets by cortical lesions -at distinctly different concentrations. In this proposal we will test in normal rats the role of this factor in maintaining these dLGN neurons during their period of natural cell death, as well as determine if the different neuron sub-populations (defined by their time of origin) also have different concentration requirements for this factor during this normal cell death period. Concentration-specific requirements for this factor in order for adult dLGN neurons to survive axotomy will also be tested in vivo, along with the correlated idea that this concentration specificity may reflect different rates of factor depletion in the different sub-populations after axotomy. Finally another important prediction of the trophic factor hypothesis - that developing neurons require specific trophic factors in order to differentiate - will be tested in vitro by determining the effect of different concentrations of the factor on relationship between the optimal outgrowth-promoting concentration and the optimal survival-promoting concentration for each population will be examined.

我们的实验室已经确定了一种活跃的神经营养因素 大鼠体内大鼠的基因皮层途径，并在此描述的研究 提案将利用此因素直接测试 中枢神经系统中的营养因子假设。 特别是我们将测试这个想法 目标衍生的分子对于生存和 背侧遗传神经元的发展的分化 核（DLGN）以及这些相同神经元之后的存活率 成熟。 此外，提出了大量努力以扩大规模 生产此因素（已经接近纯化） 氨基酸测序和单克隆抗体的产生。 这个因素是 从胚胎大鼠皮质和 diencephalon;关于其在体内作用的重要发现是 最大有效地支持不同的子的生存 发育中的DLGN神经元的种群 - 与目标分开 皮质病变 - 浓度明显不同。 在此提案中 我们将在正常大鼠中测试该因素在维持这些因素中的作用 DLGN神经元在自然细胞死亡期间以及 确定不同的神经元子群（由它们的时间定义 原点）对此因素也有不同的浓度要求 在这个正常的细胞死亡期间。 浓度特定的要求 对于这个因素，以使成年DLGN神经元生存于轴切开术将 也可以在体内进行测试，以及相关的想法 浓度特异性可能反映了因子耗竭的速率不同 在轴切开后不同的亚群中。 最后是另一个重要的 营养因子假说的预测 - 发展神经元 需要特定的营养因素才能进行区分 - 将被测试 通过确定不同浓度的影响 最佳促进生长的关系因素 每个浓度和最佳生存促进浓度 将检查人口。