Neurotrophin regulation of peripheral neurons

描述（由申请人提供）：拟定的基本假设 研究表明，神经营养因子调节成人外周神经元的活动， 神经元这些实验的总体目标是了解特定的 参与这些调节作用的机制。神经营养因子 因为神经生长因子（NGF）和神经营养因子-3（NT 3）被认为调节 神经元生长和分化的外周神经元，但其调节 成年人的作用知之甚少。的神经营养活性 神经营养因子由两种类型的跨膜受体介导--p75，低 结合所有神经营养因子的亲和受体，以及trk酪氨酸激酶 受体（即trkA、trkC），高亲和力神经营养因子受体家族， 每一种都优先结合特定的神经营养素。使用我们的体内 侧脑室注射神经生长因子模型，我们有机会测试 关于NGF对这些受体的差异调节的假说 使用形态学和分子测量。另外，我们假设 外源性NGF增强外周神经元和胶质细胞之间的相互作用， 支持细胞，提供证据表明，神经营养调节成年神经元 是由旁分泌神经元-神经胶质相互作用介导的。我们提出实验 研究交感神经和感觉神经的神经节内通讯 神经节 主要目的是：1）确定外源性NGF的影响， 交感神经元对神经营养素受体表达的传入输入; 2） 研究NGF在增强交感神经感觉和旁分泌中的作用 在上级颈神经节的相互作用和 3）检查NGF在增强交感神经感觉和 三叉神经节中的旁分泌相互作用以及 交感神经切除术这些结果将提供有关监管的信息。 神经营养因子的影响，并将为神经胶质细胞的作用提供支持 神经营养因子调节

DESCRIPTION (provided by applicant): The underlying hypothesis of the proposed studies is that neurotrophins regulate the activities of adult peripheral neurons. The overall goal of these experiments is to understand the specific mechanisms involved in these regulatory influences. Neurotrophic factors such as nerve growth factor (NGF) and neurotrophin-3 (NT3) are believed to regulate neuronal growth and differentiation of peripheral neurons, yet their regulatory role in the adult is poorly understood. The neurotrophic activities of neurotrophins are mediated by two types of transmembrane receptors--p75, low affinity receptor that binds all neurotrophins, and the trk tyrosine kinase receptor (i.e. trkA, trkC), a family of high affinity neurotrophin receptors, each of which preferentially binds a specific neurotrophin. Using our in vivo model of intracerebroventricular NGF infusion, we have the opportunity to test hypotheses regarding the differential regulation of these receptors by NGF using both morphological and molecular measures. In addition, we hypothesize that exogenous NGF enhances interactions between peripheral neurons and glial support cells, providing evidence that neurotrophin regulation of adult neurons is mediated by paracrine neuronal-glial interactions. We propose experiments that examine intraganglionic communications in both sympathetic and sensory ganglia. The primary objectives are to: 1) determine the influences of exogenous NGF and afferent input on neurotrophin receptor expression by sympathetic neurons; 2) investigate the role of NGF in the enhanced sympathosensory and paracrine interactions in the superior cervical ganglion and the effect of deafferentation; 3) examine the role of NGF on enhanced sympathosensory and paracrine interactions in the trigeminal ganglion and the effect of sympathectomy. These results will provide information regarding the regulatory influences of neurotrophins and will provide support for a role for glial cells in neurotrophin regulation.