Differential Effects of Stress on Gene Transcription Factors in Catecholaminergic Systems

Abstract

Long-term changes in catecholamine levels and expression of their biosynthetic enzymes are associated with several stress-related disorders such as elevated plasma norepinephrine in posttraumatic stress disorder and increased postmortem tyrosine hydroxylase in the locus coeruleus with major depression. Stress elevates tyrosine hydroxylase gene expression in the CNS and periphery. Increased transcriptional initiation was involved in this induction in the rat adrenal medulla and locus coeruleus in response to single as well as repeated immobilization stress (IMO). We examined the stress-triggered induction or phosphorylation of several transcription factors, which were previously shown to be able to modulate tyrosine hydroxylase transcription. A single episode of IMO triggered elevations of c-fos in both the adrenal medulla and locus coeruleus. With repeated daily IMO, Fra-2 was a major AP-1 factor induced in the adrenal medulla, but not in the locus coeruleus. Egr1 levels were markedly elevated in the adrenal medulla with both single and repeated IMO stress, but not in the locus coeruleus. In the locus coeruleus, increased phosphorylation of CREB was observed after both single and repeated IMO. Results implicate differential transcription pathways in mediating elevation of gene expression of tyrosine hydroxylase, and other target genes, in these locations.