Previous work in my laboratory demonstrated an increase in the number of fibers of primary sensory afferents in the dorsal root after unilateral spinal cord denervation. This increase is primarily in the unmyelinated fiber population and is interpreted as sprouting. In an effort to manipulate this phenomenon, the protein Nerve Growth Factor NGF) and antibodies to NGF (Anti-NGF) were given to denervated and normal neonatal rats. Work to date indicates that NGF had little effect on neuron or axon populations but after anti-NGF treatment, a population of small neurons in the dorsal root ganglion dies and the remaining neurons emit more processes than before. It is the goal of the present research proposal to pursue the extent and molecular mechanisms of the neural reorganization caused by anti-NGF in the following specific aims: 1) To determine composition and origin of sprouting fibers in the spinal cord. 2) To determine molecular markers for the sprouted presynaptic endings and postsynaptic structures in the dorsal horn. 3) To determine which cell populations synthesize NGF, have receptors for NGF, and accumulate and bind NGF in the central and peripheral nervous systems. Techniques include ultrastructural stereology, immunocytochemistry, autoradiography and in situ hybridization. This information will contribute to the understanding of molecular mechanisms underlying the selective death and sprouting of neuronal populations in response to exogenous factors. This knowledge will contribute to the use of exogenous drugs toward manipulations of specific neuronal populations in clinical situations.
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