Stress induced changes in gene expression in catecholaminergic systems
Chronic stress is associated with increased expression and transcription of genes for tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) in key stress responsive catecholaminergic (CA) areas including the adrenal medulla and locus coeruleus (LC). To study the mechanism of stress triggered transcriptional responses, Sprague Dawley male rats were exposed to single (up to 2 hrs) or repeated (up to 7 consecutive days, 2 hr each) immobilization stress (IMO). Various CA tissues were taken to prepare RNA used for quantitative RT-PCR and microarray profiling, or proteins for western blots and immunocytochemistry. In some experiments, rats were pre-exposed to chronic cold stress prior to the IMO.
In LC,TH and DBH gene transcription were induced by single and repeated IMO. Repeated IMO, elicited different kinetics or magnitude of expression of various transcription factors including cFos, Fra2 and CREB and triggered activation of several upstream MAP kinases.
In adrenal medulla, Egr1 was also markedly induced. Microarray profiling of RNA from adrenal medulla revealed a number of additional transcription factors including CREM, ATF and Nurr1 family members, which may regulate TH transcription, and led us to propose differential signalling pathways with single and repeated IMO. Pre-exposure to cold stress led to a potentiation of the response to IMO stress including more pronounced Egr1 induction and phosphorylation of CREB and Fra2.
These distinct alterations following repeated, compared to single stress, may be involved in mediating long lasting neuronal remodeling and the conversion of acute beneficial responses to stress are converted into prolonged adaptive or maladaptive responses.