ROLE OF FGF IN NEURONAL INJURY

FGF 在神经元损伤中的作用

• 批准号: 6193839
• 负责人: FELIX P ECKENSTEIN
• 金额: $ 26.43万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-05 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6193839
• 关键词: cell cycle; fibroblast growth factor; genetically modified animals; growth factor receptors; laboratory mouse; motor neurons; nervous system regeneration; neural plasticity; receptor expression

DESCRIPTION (adapted from applicant's abstract): Acidic fibroblastic growth factor (FGF1) is a potent neurotrophic factor for most neuronal populations and a mitogen for many nonneuronal cell types. In the adult nervous system, specific neuronal populations express FGF1 in high levels, including motoneurons, basal forebrain cholinergic neurons and substantia nigra dopaminergic neurons. FGF1 lacks a hydrophobic signal peptide sequence, is not sorted to the secretory pathway, and may not be efficiently released from unstimulated healthy neurons. It is our hypothesis that injury causes the release of sufficient amounts of FGF1 to result in the activation of widely expressed transmembrane FGF receptors (FGFRs). This activation then provides autocrine neurotrophic support to damaged neurons and a paracrine activation signal to glial cells adjacent tot he damaged neurons. This hypothesis suggests that FGF1 is of great importance for the maintenance, plasticity and regeneration of motoneurons. Novel tools, including antibodies that specifically recognize the activated form of FGFRs and FGF1 knockout, FGF2 (a close relative of FGF1) knockout and FGF1/FGF2 double knockout mice will be used to test this hypothetical role of FGF1.

描述（改编自申请人的摘要）：酸性成纤维细胞生长 因子（FGF1）对于大多数神经元群来说是一种有效的神经营养因子，并且 许多非神经元细胞类型的有丝分裂原。在成人的神经系统中， 特定神经元群体高水平表达 FGF1，包括 运动神经元、基底前脑胆碱能神经元和黑质 多巴胺能神经元。 FGF1 缺乏疏水性信号肽序列，不是 分选至分泌途径，并且可能无法有效地从 未受刺激的健康神经元。我们的假设是伤害导致 释放足量的 FGF1，从而广泛激活 表达跨膜 FGF 受体 (FGFR)。此激活然后提供 对受损神经元的自分泌神经营养支持和旁分泌激活 向邻近受损神经元的神经胶质细胞发出信号。这个假设表明 FGF1对于维持、可塑性和 运动神经元的再生。新工具，包括抗体 特异性识别 FGFR 的激活形式和 FGF1 敲除后的 FGF2（a FGF1) 敲除小鼠和 FGF1/FGF2 双敲除小鼠的近亲将是 用于测试 FGF1 的这一假设作用。