Stress induces the expression of heterotrimeric G protein β subunits and the phosphorylation of PKB/Akt and ERK1/2 in rat brain

Various heterotrimeric G protein beta gamma subunits (G beta gamma) are region-specifically expressed in brain where associated with "stress-axis", however, the role of G beta gamma-mediated signaling in regulating stress is unknown. This study was designed to examine the changes of G beta gamma expression and G beta gamma-mediated signaling in rat brain by stress. Experimental stress was induced by immobilization (2 h/day for 7 days) and the level of mRNAs and proteins for G beta(1-5), and the phosphorylation of PKB/Akt (phosphatidylinositol 3-kinase-linked protein kinase B) and ERK1/2 (extracellular signal-regulated kinase 1/2) were measured in five different regions of rat brain including frontal cortex, striatum, hypothalamus, hippocampus, and cerebellum. As compared in not-handled non-stressed animals, the expression of both mRNAs and proteins for G beta(1-5) in brain regions associated with stress was increased in stressed animals. Especially, a significant increase in G beta s immunoreactivity in the caudate putamen, the paraventricular nucleus of the hypothalamus (PVN), and the dentate gyrus of the hippocampus (DG) of stressed rats was observed. Stress significantly induced the phosphorylation of PKB/Akt and ERK1/2 in striatum, hypothalamus and hippocampus. Therefore, these results suggest that stress may activate, at least in part, the G beta gamma-mediated PKB/Akt and ERK1/2 signaling pathway by increasing the expression of G beta s to regulate the physiological responses. (c) 2006 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.