TROPHIC FACTOR EXPRESSION BY ENSHEATHING GLIA

通过鞘内神经胶质细胞表达营养因子

• 批准号: 2658775
• 负责人: KATHLEEN M GUTHRIE
• 金额: $ 5.25万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1999-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2658775
• 关键词: developmental neurobiology; fibroblast growth factor; glia; growth factor receptors; laboratory rat; nervous system regeneration; neurotrophic factors; newborn animals; olfactory nerve; receptor expression

Neurotrophic interactions are critical to many developmental processes in the nervous system and are thought to contribute to regenerative events as well. Glial cells are intimately involved in nerve development and may provide appropriate cell substrates and trophic support for axon outgrowth and guidance. The mammalian olfactory nerve contains a unique type of non-myelinating glial cell, termed the ensheathing cell, with phenotypic traits of both Schwann cells and astrocytes. This nerve is unusual in that following injury, it can regenerate its central projections to the olfactory bulb via replacement of sensory neurons in the olfactory epithelium by basal cells which differentiate into sensory neurons. This regenerative capacity may in part be due to specific environmental cues provided to the growing afferents by the ensheathing cells. Little is currently known about potential trophic actions of ensheathing cells on olfactory axon growth, but studies by the applicant have shown that ensheathing glia in the adult rat olfactory bulb express high levels of the neurotrophic factors basic fibroblast growth factor (bFGF) and ciliary neurotrophic factor (CNTF). Both of these factors have been implicated in regeneration of peripheral nerve and central axonal sprouting. These data suggest that expression of neurotrophic factors by ensheathing glia may contribute to axon growth in the olfactory system. The goals of the proposed research are to test aspects Of this hypothesis. The first goal is to characterize expression of CNTF, bFGF and acidic FGF in the developing olfactory system to determine if ensheathing cell expression of trophic factors is correlated with outgrowth of developing sensory axons. The second goal will be to determine if olfactory sensory neurons express appropriate receptors for these trophic factors during this time. The third aim is to determine if ensheathing glia and sensory neurons undergo changes in expression of trophic factors and receptors during periods of olfactory nerve degeneration and regeneration in lesioned adult rats. The final aim is to establish cultures of ensheathing glia from the neonatal rat and to characterize expression of trophic factors by these cells in vitro. Results of these studies could provide valuable insights into potential glial-dependent trophic mechanisms which promote nerve growth.

神经营养的相互作用对于许多发展过程至关重要 在神经系统中，被认为有助于再生 事件也是如此。神经胶质细胞与神经密切相关 开发并可能提供适当的细胞底物和营养 支持轴突的生长和指导。哺乳动物嗅觉神经 包含独特类型的非层状神经胶质细胞，称为 分院细胞，具有Schwann细胞的表型性状和 星形胶质细胞。这种神经是不寻常的，因为受伤后可以 通过对嗅球的中心预测通过 用基础代替嗅觉上皮中的感觉神经元 分化为感觉神经元的细胞。这种再生 容量可能部分是由于提供给的特定环境提示 通过分院细胞的成长传入。目前几乎没有 已经知道了嗅觉细胞对嗅觉的潜在营养作用 轴突生长，但申请人的研究表明了 成年大鼠嗅球中的神经胶质表达高水平 神经营养因子碱性成纤维细胞生长因子（BFGF）和睫状 神经营养因子（CNTF）。这两个因素都被暗示 在周围神经和中央轴突发芽的再生中。 这些数据表明，通过 开放胶质神经胶质可能有助于嗅觉系统的轴突生长。 拟议的研究的目标是测试此方面 假设。第一个目标是表征CNTF，BFGF的表达 和发育中的嗅觉系统中的酸性FGF，以确定是否是否 营养因子的振兴细胞表达与 发展感官轴突的产物。第二个目标是 确定嗅觉感觉神经元是否表达适当的受体 在这段时间内这些营养因素。第三个目标是 确定开发神经胶质和感觉神经元是否发生变化 嗅觉期间的营养因子和受体的表达 病变的成年大鼠的神经变性和再生。决赛 目的是从新生大鼠建立培养神经胶质的培养物 并表征这些细胞在 体外。这些研究的结果可以为您提供宝贵的见解 潜在的神经胶质依赖性营养机制，促进神经 生长。