Neurotrophin regulation of peripheral neurons

神经营养蛋白对周围神经元的调节

• 批准号: 6457420
• 负责人: LORI G ISAACSON
• 金额: $ 14万
• 依托单位: MIAMI UNIVERSITY OXFORD
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6457420
• 关键词: biological signal transduction; cell cell interaction; cell differentiation; cell growth regulation; densitometry; enzyme linked immunosorbent assay; glia; growth factor receptors; immunocytochemistry; laboratory rat; messenger RNA; neurons; neurophysiology; neurotrophic factors; peripheral nervous system; polymerase chain reaction; receptor expression; superior cervical ganglion

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.

描述(申请人提供)：建议的基本假设 研究表明，神经营养因子调节成人外周血的活动 神经元。这些实验的总体目标是了解特定的 参与这些监管影响的机制。神经营养因子，如 作为神经生长因子(NGF)和神经营养因子-3(NT3)被认为是调节 外周神经元的生长和分化及其调控 人们对成人的作用知之甚少。海藻毒素的神经营养活性 神经营养因子由两种跨膜受体介导--p75，low 结合所有神经营养素的亲和力受体和trk酪氨酸激酶 受体(即TrkA、trkC)，是一类高亲和力的神经营养因子受体家族， 每一个都优先结合一种特定的神经营养因子。利用我们在体内的 脑室内注射NGF的模型，我们有机会测试 神经生长因子对这些受体的差异性调控假说 同时使用形态和分子测量方法。此外，我们假设 外源性NGF增强外周神经元与神经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因子对成年神经元的调节 是由旁分泌神经元-神经胶质细胞相互作用所介导的。我们建议进行实验 研究交感神经和感觉神经的节内通讯 神经节。 主要目标是：1)确定外源性NGF和 传入信息对交感神经元神经营养素受体表达的影响 探讨神经生长因子在交感和旁分泌增强中的作用 颈上神经节的相互作用及电针的影响 3)检测NGF在增强交感神经感觉和 三叉神经节旁分泌相互作用及其影响 交感神经切除。这些结果将提供有关监管机构 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 神经营养因子的调节。