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.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Small Research Grants (R03)
Project #
1R03TW000984-01
Application #
2695501
Study Section
International and Cooperative Projects 1 Study Section (ICP)
Program Officer
Michels, Kathleen M
Project Start
1998-09-30
Project End
2001-09-29
Budget Start
1998-09-30
Budget End
1999-09-29
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
New York Medical College
Department
Biochemistry
Type
Schools of Medicine
DUNS #
City
Valhalla
State
NY
Country
United States
Zip Code
10595
Micutkova, L; Rychkova, N; Sabban, E L et al. (2003) Quantitation of changes in gene expression of norepinephrine biosynthetic enzymes in rat stellate ganglia induced by stress. Neurochem Int 43:235-42
Kocan, J; Lencesova, L; Kiss, A et al. (2002) Distribution of neuronal and non-neuronal spliced variants of type 1 IP(3)-receptor in rat hypothalamus and brain stem. Neurochem Int 41:65-70
Jelokova, J; Rusnak, M; Kubovcakova, L et al. (2002) Stress increases gene expression of phenylethanolamine N-methyltransferase in spleen of rats via pituitary-adrenocortical mechanism. Psychoneuroendocrinology 27:619-33
Kubovcakova, Lucia; Sabban, Esther L; Kvetnansky, Richard et al. (2002) Comparative study of catecholamine synthesizing enzymes in adrenal medulla of CRH knock-out mice, their CRH (+/+) mates and Sprague-Dawley rats. Endocr Regul 36:107-13
Kubovcakova, L; Micutkova, L; Sabban, E L et al. (2001) Identification of tyrosine hydroxylase gene expression in rat spleen. Neurosci Lett 310:157-60
Krizanova, O; Micutkova, L; Jelokova, J et al. (2001) Existence of cardiac PNMT mRNA in adult rats: elevation by stress in a glucocorticoid-dependent manner. Am J Physiol Heart Circ Physiol 281:H1372-9