NGF effects on axonal growth in CNS white matter

NGF 对中枢神经系统白质轴突生长的影响

• 批准号: 6557886
• 负责人: Keith Alan Crutcher
• 金额: $ 29.17万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6557886
• 关键词: axon; enzyme linked immunosorbent assay; genetically modified animals; glial fibrillary acidic protein; growth factor receptors; immunocytochemistry; laboratory mouse; nerve growth factors; nervous system regeneration; tissue /cell culture; western blottings

DESCRIPTION (provided by applicant): Axonal regeneration has now been demonstrated to occur in regions of the CNS where it was formerly thought to be impossible. These dramatic examples of successful regrowth have come from studies in which the influence of both inhibitors and promoters of neurite growth have been examined. The importance of neuronal growth state on regeneration success has recently been demonstrated in studies of optic nerve regeneration. Collectively, these results point to the importance of factors that normally stimulate growth in overcoming the non-permissive features of CNS white matter. The work proposed here will take advantage of techniques that have been developed in this laboratory over several years that permit assessment of the role of NGF in stimulating axonal growth within the CNS. Transgenic mice in which NGF is over-expressed under the control of an astrocyte-specific promoter (GFAP), will be used for both in vitro and in vivo studies of axonal growth in CNS white matter. In vivo studies of sympathetic axonal growth within CNS regions of such mice will be carried out to determine the extent to which ectopic expression of NGF modifies the growth of these aberrant fibers. In addition, tissue section culture studies will be carried out to determine whether NGF, either applied exogenously or expressed transgenically, will modify the generally non-permissive nature of CNS white matter in supporting axonal growth. Finally, the role of p75, the low-affinity NGF receptor, in modifying axonal growth of NGF-responsive neurons in CNS white matter will be studied through a series of transplant and tissue culture approaches using transgenic mice in which p75 is deficient in the presence of NGF overexpression. The primary goal is to study the role of neurotrophic factors in stimulating axonal regeneration within CNS white matter.

描述（由申请人提供）：现已证明轴突再生发生在中枢神经系统的地区，以前被认为是不可能的。这些成功再生的戏剧性例子来自研究，其中研究了抑制剂和神经突增长的启动子的影响。神经元生长状态对再生成功的重要性最近在视神经再生研究中得到了证明。总的来说，这些结果表明，在克服CNS白质的非允许特征时，通常会刺激生长的因素的重要性。 这里提出的工作将利用几年来该实验室中开发的技术，这些技术允许评估NGF在刺激CNS内轴突生长中的作用。在星形胶质细胞特异性启动子（GFAP）控制下NGF过表达的转基因小鼠将用于体外和体内研究中枢神经系统白质的轴突生长研究。将进行此类小鼠中枢神经系统区域内的交感神经轴突生长的体内研究，以确定NGF的异位表达修饰这些异常纤维的生长的程度。 此外，将进行组织截面培养研究，以确定NGF是外源或转基因表达是否会改变CNS白质在支持轴突生长方面的普遍非耐受性。 最后，将通过一系列使用转基因小鼠进行一系列移植和组织培养方法来研究CNS白质NGF响应​​神经元在CNS白质中NGF响应​​神经元的轴突生长p75的作用，其中P75在NGF过表达的情况下缺乏P75。 主要目标是研究神经营养因素在刺激CNS白质中轴突再生中的作用。