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.
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