Single and repeated immobilization stress differentially trigger induction and phosphorylation of several transcription factors and mitogen-activated protein kinases in the rat locus coeruleus
Article first published online: 25 AUG 2005
Journal of Neurochemistry
Volume 95, Issue 2, pages 484–498, October 2005
How to Cite
Hebert, M. A., Serova, L. I. and Sabban, E. L. (2005), Single and repeated immobilization stress differentially trigger induction and phosphorylation of several transcription factors and mitogen-activated protein kinases in the rat locus coeruleus. Journal of Neurochemistry, 95: 484–498. doi: 10.1111/j.1471-4159.2005.03386.x
- Issue published online: 12 SEP 2005
- Article first published online: 25 AUG 2005
- Received January 19, 2005; revised manuscript received April 19, 2005; accepted June 7, 2005.
- cAmp-response element binding protein;
- locus coeruleus;
- mitogen activated protein kinases;
- transcription factors;
- tyrosine hydroxylase
The locus coeruleus (LC) is a critical stress-responsive location that mediates many of the responses to stress. We used immunoblotting and immunohistochemistry to investigate changes in induction and phosphorylation of several transcription factors and kinases in the LC that may mediate the stress-triggered induction of tyrosine hydroxylase (TH) transcription. Rats were exposed to single or repeated immobilization stress (IMO) for brief (5 min), intermediate (30 min) or sustained (2 h) duration. Single IMO elicited rapid induction of c-Fos and phosphorylation of cyclic AMP response element-binding protein (CREB) without changing the expression of early growth response (Egr)1, Fos-related antigen (Fra)-2 or phosphorylated activating transcription factor-2. Repeated IMO triggered increased phosphorylation and levels of CREB along with transient induction of c-Fos and increased Fra-2 expression. Several mitogen-activated protein kinases were activated by repeated IMO, shown by increased phosphorylation of p38, c-Jun N-terminal kinase (JNK)1/2/3 and extracellular signal-regulated kinase (ERK1/2). ERK1 was the major isoform expressed, and ERK2 the predominant isoform phosphorylated. Repeated IMO elicited hyperphosphorylation of ERK1/2 selectively in TH immunoreactive neurons, with substantial nuclear localization. These distinct alterations in transcriptional pathways following repeated compared with single stress may be involved in mediating long-lasting neuronal remodeling and are implicated in the mechanisms by which acute beneficial responses to stress are converted into prolonged adaptive or maladaptive responses.