This application is for the continuation of a research program on the recovery of function after neural damage. The proposed experiments will be performed on the peripheral nervous system due to its relative anatomical and biochemical simplicity and to its accessibility; however, we expect many of our findings to be applicable to the central nervous system as well. Biochemical changes in the cell bodies of peripheral neurons are thought to be related to survival and regeneration of the damaged neurons. In the present proposal, we focus on increases in the expression of certain neuropeptides in peripheral neurons after axotomy, with particular emphasis on sympathetic neurons in the rat superior cervical ganglion (SCG). Recent evidence suggests that some of these neuropeptides may act as trophic agents in the nervous system. A combination of biochemical and histochemical techniques, including radioimmunoassay, Northern blot analysis, immunohistochemistry and in situ hybridization, will be used to measure specific neuropeptides and their associated mRNA's.
The specific aims of the proposal are l)to determine the neuropeptide phenotype (s) of neurons in the SCG after axotomy by assaying immunoreactivity for ten peptides selected based on strict criteria, 2)to compare this phenotype to the neuropeptide phenotypes of axotomized sensory and motor neurons, 3)to examine whether changes in the level of peptides in the SCG are accompanied by changes in their mRNA's, 4)to investigate whether similar changes in peptide expression in sympathetic neurons are elicited by other manipulations that interfere with communication between sympathetic neurons and their target tissues and to determine 5)the involvement of specific differentiation factors and 6)non-neuronal cells in these changes in expression. The long term objective of this research is to understand the molecular and cellular mechanisms that promote or inhibit functional recovery after neural damage, such as that caused by stroke, trauma, and degenerative neurological disease. In addition, the results will be relevant to more general issues of the regulation of gene expression in the nervous system.
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