Abstract
It is postulated that alterations in neuronal gene expression mediated by an activation of cAMP response element binding protein (CREB) may play an important role in the pathogenesis of stress-related psychiatric disorders, such as major depression and posttraumatic stress disorder. We examined the influence of restraint stress on CREB phosphorylation in rat frontal cortex and hippocampus. Restraint stress significantly increased the levels of phospho-CREB (p-CREB) in both brain regions. In addition, the marked induction of p-CREB expression in response to acute restraint stress was found in rats vulnerable to chronic overcrowding stress. Pretreatment with FK506 significantly upregulated the induction of c-fos mRNA in response to acute stress. On the other hand, we also examined the effect of stress on the expression and the serine/threonine phosphatase activity of calcineurin to elucidate the influence of stress on the dephosphorylation of p-CREB. Whereas stress had no change in the levels of calcineurin mRNA, the activity of calcineurin was significantly upregulated. Taken together, these findings suggest that the induction of CREB phosphorylation and the changes in CRE-mediated gene expression may be, at least in part, involved in the pathogenesis of stress-related psychiatric disorders.
