MOLECULAR MECHANISMS OF SPROUTING IN THE SPINAL CORD

脊髓发芽的分子机制

• 批准号: 3738159
• 负责人: CLAIRE E. HULSEBOSCH
• 金额: --
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3738159
• 关键词: afferent nerve; animal age group; antibody; autoradiography; axon; cell type; developmental neurobiology; dorsal column; electron microscopy; gene expression; growth factor receptors; immunocytochemistry; in situ hybridization; laboratory rabbit; laboratory rat; longitudinal animal study; messenger RNA; microscopy; monoclonal antibody; nervous system regeneration; neuronal guidance; neurotrophic factors; peripheral nervous system; spinal cord; synapses; synaptogenesis

Previous work demonstrates that primary afferent axons sprout intraspinally in response to postnatal treatment with antibodies against Nerve Growth Factor (ANTI-NGF). I hypothesize that ANTI-NGF induces primary afferent intraspinal sprouting in response to NGF deprivation centrally. Also, recent biochemical studied demonstrate that central concentrations of macromolecules in the NGF pathway decrease as animals age and other studies demonstrate primary afferent sprouting is age related. Thus, I further hypothesize that macromolecules in the NGF pathway are developmentally regulated and the developmental differences are the basis for the primary afferent sprouting. These experiments are designed to compare results of ANTI-NGF treated rats to results from rats of different developmental ages, including adult and aged. Specific Aim 1. To determine the distribution, density and cell types which bind ANTI-NGF in the CNS. Specific Aim 2. To determine the distribution, density and cell types which express NGF and the receptor of NGF (NGF-R). Specific Aim 3. To determine the distribution, density and cell types which contain mRNA for expression of NGF and NGF-R proteins. Techniques which will be used include histological and ultrastructural immunocytochemistry, autoradiography and in situ hybridization. This cytological localization will be important in determining the regions and cell populations involved in NGF interactions with primary afferent neurons and will bear on development, regeneration and aging. Additionally, this information will be important in therapy toward manipulations of specific CNS neuronal populations.

以前的工作表明，初级传入轴突在脊髓内萌发 出生后使用抗神经生长抗体治疗的反应 因子(抗NGF)。我推测抗NGF诱导初级传入 脊髓内发芽是对中枢神经生长因子剥夺的反应。另外， 最近的生化研究表明，中枢浓度的 随着动物年龄的增长和其他研究，NGF途径中的大分子减少 证明初级传入发芽与年龄有关。因此，我进一步 假设NGF途径中的大分子是发育中的 规律性和发展性差异是小学生 传入性萌发。这些实验旨在比较 抗NGF对不同发育期大鼠的治疗效果， 包括成人和老年人。 具体目标1.确定细胞的分布、密度和类型 它与中枢神经系统中的抗NGF结合。 具体目标2.确定细胞的分布、密度和类型 表达NGF及其受体(NGF-R)。 具体目标3.确定细胞的分布、密度和类型 它含有表达NGF和NGF-R蛋白的mRNA。 将使用的技术包括组织学和超微结构 免疫细胞化学、放射自显影和原位杂交。这 细胞学定位在确定区域和 参与NGF与初级传入神经元相互作用的细胞群 并将承担发展，再生和老化。此外，这一点 信息在针对特定操作的治疗中将是重要的 中枢神经元群。