Nerve growth factor (NGF) is essential for the survival of embryonic sensory neurons in dorsal root ganglia (DRG). Recent observations indicate that the role of NGF is more complex and probably more important throughout the life of a DRG neuron than previously thought. We have found: 1) I125-NGF is retrogradely transported from the spinal cord to the DRG; 2) cutting the central process of DRG in newborn rats results in massive neuronal death; 3) exogenous systemic NGF prevents the cell death produced by lesions of the central or peripheral process of the DRG; and 4) intraspinal tracts bears NGF receptors. These results show that the central process of sensory neurons is important in providing trophic support, at least during development and suggest a physiological role for NGF in that support. We will systematically characterize the effects of lesioning the central, the peripheral, or combined central/peripheral lesions on DRG neurons. We will examine cell survival, and morphological (chromtolysis, etc.) and biochemical changes (peptide levels, lysosomal markers) caused by these lesions in animals of various ages. We will thereby determine the relative role of the central vs. peripheral process in the trophic support of sensory neurons at different stages of development. We will examine these same parameters in animals deprived of NGF by anti-NGF to assess the physiological role of NGF in the response to these lesions in animals of various ages. We will examine the ability of exogenous, systemic or locally applied NGF to prevent cell death or modulate the injury response to the lesion and thereby assess the pharmacological potential of NGF to amelionate those injuries. We will quantify by immunoassay the amount of NGF being retrogradely transported via the central and peripheral process of DRG neurons in animals of different ages and correlate these values with the relative importance of the central vs. peripheral process at different stages of development. We will measure NGF levels in normal and denervated (dorsal rhizotomized) spinal cord. Lastly, we will examine and identify by autoradiographic and immunohistochemical methods the intraspinal tracts found to bear NGF receptors and look for retrograde transport of I125-NGF in specific CNS tracts. These experiments will increase our understanding of the role of the central process and of NGF in sensory trophic support and will assess possible roles of NGF in the CNS.
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