MOLECULAR MECHANISMS OF SPROUTING IN THE SPINAL CORD

先前的工作表明初级传入轴突在椎管内萌芽 针对神经生长抗体的产后治疗 因子（抗 NGF）。 我假设 ANTI-NGF 诱导初级传入神经 椎管内出芽是对 NGF 剥夺的集中反应。 另外， 最近的生化研究表明，中心浓度 NGF 通路中的大分子随着动物年龄的增长和其他研究而减少 证明初级传入神经萌芽与年龄相关。 于是，我进一步 假设 NGF 通路中的大分子在发育过程中 调节和发育差异是主要的基础 传入萌芽。 这些实验旨在比较结果 ANTI-NGF 治疗大鼠得到不同发育年龄大鼠的结果， 包括成人和老年人。 具体目标 1. 确定分布、密度和细胞类型 其结合中枢神经系统中的抗NGF。 具体目标 2. 确定分布、密度和细胞类型 表达 NGF 和 NGF 受体 (NGF-R)。 具体目标 3. 确定分布、密度和细胞类型 其中含有用于表达 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。 这个 细胞学定位对于确定区域和 参与 NGF 与初级传入神经元相互作用的细胞群 并将影响发育、再生和衰老。 另外，这 信息对于针对特定操作的治疗非常重要 中枢神经系统神经元群。

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.