MECHANISMS OF STRESS SPECIFIC CHANGES IN GENE EXPRESSION

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DESCRIPTION Early responses to stress include activation of noradrenergic neurons of the locus coeruleus, and the sympathetic neuronal and adrenomedullary systems, resulting in production of the central and peripheral catecholamines norepinephrine and epinephrine. Stress also elevates gene expression for catecholamine biosynthetic enzymes, and there are gene-, tissue-, and stressor-specific differences in these responses to stress. The proposal investigates the mechanisms of regulation of gene expression of catecholamine biosynthetic enzymes (TH, DBH, and PNMT) in vivo in the adrenal medulla, sympathetic ganglia, and in different brain areas of rats exposed acutely, repeatedly or chronically to various stressors. Specific aims are: (1) determine effects of different stressors on TH, DBH, and PNMT gene expression, (2) determine dependence of single or repeated stress-elicited effects of TH, DBH, and PNMT expression on the transcription factor c-fos, (3) characterize the basis for differential regulation of TH and DBH gene expression in sympathetic ganglia compared to adrenal medulla, (4) determine effects of prior chronic or repeated exposure to stressors in the response to a novel stressor and (5) determine if TH and DBH gene expression is detectable in brain areas other than the major catecholaminergic cell fields, and if expression in these areas is regulated by stressors.