The effect of stress mediators following the stress period and addition time is a controversial issue until now. Thus, we aim to clarify the differential effects of single restraint stress (SS) or repeated restraint stress (RS) on kainic acid (KA)-induced neuronal death especially as addressing not only the role of glucocorticoid (Gc) and its receptor but also the signal pathway leading to cAMP response element binding protein phosphorylation (pCREB) and its functional role during stress. In the present study, we found that although RS did not show any difference on serum Gc level and hippocampal Gc receptor level compared to SS, SS exacerbated KA-induced neuronal death in hippocampal CA3 region, but RS did not. Moreover, pre-treatment with RU 38486 (Gc receptor antagonist) abolished the effect of SS on KA-induced neuronal death without an effect on KA toxicity itself. Furthermore, RS aggravates KA-induced neuronal death when CREB phosphorylation was deprived by KN-93 (calcium/calmodulindependent protein kinase II inhibitor). However, other signal molecules inhibitors such as PD98059 (MEK1/2 inhibitor) and SP600125 (p-p38 inhibitor) have no effect on KA-induced neuronal death after RS although these signal molecule were increased during SS or RS. These findings suggest that pCREB expression via calcium/calmodulin-dependent protein kinase II phosphorylation during RS comprise one of the balancers against Gc induced by stress. Keywords: hippocampus, kainic acid, neuronal death, phosphorylated calcium/calmodulin dependent protein kinase II, phosphorylated cyclic-AMP response element binding protein, stress.
Several ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, Rg1 and Rg3) are neuroprotective and antinociceptive agents. In this study, we assessed the effects of these ginsenosides following intracerebroventricular (i.c.v.) administration on the nociceptive behaviors induced by intrathecal injection of pro-inflammatory cytokines (tumor necrosis factor-a (TNF-alpha), interleukin-1 beta (IL-1 beta), and interferon-gamma (IFN-gamma)). The ginsenosides, Rb1, Rb2, Rc, Rd, Re, Rf and Rg1, significantly attenuated the nociceptive behavior induced by TNF-alpha, IL-1 beta, and IFN-gamma injection, but ginsenoside-Rg3 did not. These results suggest that several ginsenosides may regulate the nociceptive processing induced by pro-inflammatory cytokines.
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