AXONAL GROWTH IN THE MATURE CENTRAL NERVOUS SYSTEM

哪些因素调节成熟脑和脊髓中的神经元可塑性 电源线？这个问题是旨在促进 中枢神经系统(CNS)的损伤恢复能力 由中风、创伤或退行性疾病引起。轴突生长和 成熟的中枢神经系统可形成突触。潜在的机制 然而，这样的增长并不明朗。颅底前脑的损伤 大鼠(已知在阿尔茨海默病中受影响的大脑区域) 导致血管自主神经纤维(交感神经轴突)的生长 进入海马体结构，这种反应显著降低 在年迈的动物身上。幼鼠体内轴突生长的例子是 在此之前，脑内神经生长因子(NGF)的数量增加 发生增长的区域。然而，我们已经证明，全球 外源性NGF的输注不足以诱导交感神经内生 隔纤维的存在表明局部NGF的升高 可能需要用来诱导萌发。在接下来的五年中，有两个目标 年限将决定NGF在未来几年内是否在当地可用 海马区结构决定交感神经向内生长的地形 以及鼻中隔损伤是否改变了脑组织的促生长能力 在培养中用作底物的海马区组织切片。三分之一 目标是确定与年龄相关的交感神经功能是否下降 发芽是由于隔膜后营养因子诱导减少所致 去神经和/或组织底物特性的改变。这就产生了 从我们的发现来看，总的NGF没有随着年龄的增长而下降 在大鼠海马区的活动。第四个目标是确定 老年交感神经元对外源性神经生长因子的反应性 假设萌芽减少的部分原因是反应性降低 老化的交感神经元对神经生长因子的作用。所有的实验都是为了 揭示有关调节轴突生长的因素的信息 在成熟和老化的神经系统中。

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.