AXONAL GROWTH IN THE MATURE CENTRAL NERVOUS SYSTEM

成熟中枢神经系统的轴突生长

• 批准号: 2263154
• 负责人: Keith Alan Crutcher
• 金额: $ 14.69万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-01 至 1998-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2263154
• 关键词: age difference; astrocytes; axon; bioassay; brain injury; brain septal area; central nervous system; cryostat; denervation; electron microscopy; enzyme linked immunosorbent assay; hippocampus; laboratory rat; nervous system regeneration; neural plasticity; neurogenesis; neurotrophic factors; sympathetic nervous system; tissue /cell culture

What factors regulate neuronal plasticity in the mature brain and spinal cord? This question is at the center of research that seeks to promote the ability of the central nervous system (CNS) to recover from injury resulting from stroke, trauma or degenerative disease. Axonal growth and synapse formation can occur in the mature CNS. The mechanisms underlying such growth, however, are not clear. Damage to the basal forebrain of the rat (brain regions that are known to be affected in Alzheimer's disease) results in the growth of vascular autonomic fibers (sympathetic axons) into the hippocampal formation, a response that is significantly reduced in the aged animal. This example of axonal growth within the young rat is preceded by an increase in the amount of Nerve Growth Factor (NGF) in the region where growth occurs. However, we have demonstrated that global infusion of exogenous NGF is not sufficient to induce sympathetic ingrowth in the presence of septal fibers suggesting that local elevation of NGF may be required to elicit sprouting. Two of the goals over the next five years are to determine whether local availability of NGF within the hippocampal formation determines the topography of sympathetic ingrowth and whether septal lesions alter the growth-promoting ability of hippocampal tissue sections when used as a substrate in culture. A third goal is to determine whether the age-related decline in sympathetic sprouting is due to reduced trophic factor induction following septal denervation and/or alterations in tissue substrate properties. This arises from our finding that there is no age-related decline in total NGF activity in the rat hippocampal formation. The fourth goal is to determine the responsivity of aged sympathetic neurons to exogenous NGF to test the hypothesis that reduced sprouting is partly due to reduced responsiveness of aged sympathetic neurons to NGF. All of the experiments are designed to reveal information regarding the factors that regulate axonal growth within the mature and aging nervous system.

哪些因素调节成熟大脑和脊柱中的神经元可塑性 绳索？这个问题是研究的中心，试图促进 中枢神经系统（CNS）从受伤中恢复的能力 由中风，创伤或退化性疾病引起。轴突生长和 突触形成可能发生在成熟的中枢神经系统中。基础机制 但是，这种增长尚不清楚。损坏了基础前脑的损害 大鼠（已知在阿尔茨海默氏病受到影响的大脑区域） 导致血管纤维的生长（交感轴突） 进入海马形成，这种反应显着降低 在老年动物中。年轻大鼠内轴突生长的例子是 在此之前，在 发生生长的地区。但是，我们已经证明了全球 输注外源性NGF不足以引起交感神经 在存在间隔纤维的情况下，表明NGF的局部升高 可能需要引起发芽。接下来的五个目标中的两个 多年是确定NGF在 海马形成确定交感神经的地形 以及间隔病变是否改变了促进生长的能力 海马组织切片用作培养物中的底物。第三 目标是确定同情年龄相关的年龄下降 发芽是由于隔离后的营养因子诱导降低而引起的 组织底物特性的神经保护和/或改变。这出现了 从我们的发现，NGF总数没有与年龄相关的下降 大鼠海马形成的活性。第四个目标是确定 老年交感神经元对外源性NGF的反应性测试 假设减少发芽是部分原因是响应能力降低 NGF的老年交感神经元。所有实验都设计为 揭示有关调节轴突生长的因素的信息 在成熟和衰老的神经系统中。