Acute p38-mediated inhibition of NMDA-induced outward currents in hippocampal CA1 neurons by interleukin-1β

Neurobiology of Disease

Xia Liu¹  Zhou Wu¹  Yoshinori Hayashi¹  Ruoyu Zhang¹  Hiroshi Nakanishi¹  Li Sun¹  Susumu Koyama² 

[1] Department of Aging Science and Pharmacology, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan;Department of Psychosomatic Medicine, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan;

关键词: IL-1β;    IL-18;    IL-1RI;    NMDA;    p38 MAP kinase;    Microglia;   

DOI  :  

来源: DOAJ

【 摘 要 】

Interleukin-1β (IL-1β) is a potent pro-inflammatory cytokine that is primarily produced by microglia in the brain. IL-1β inhibits N-methyl-d-aspartate (NMDA)-induced outward currents (INMDA-OUT) through IL-1 type I receptor (IL-1RI) in hippocampal CA1 neurons (Zhang, R., Yamada, J., Hayashi, Y., Wu, Z, Koyama, S., Nakanishi, H., 2008. Inhibition of NMDA-induced outward currents by interleukin-1β in hippocampal neurons, Biochem. Biophys. Res. Commun. 372, 816–820). Although IL-1RI is associated with mitogen-activated protein kinases, their involvement in the effect of IL-1β on INMDA-OUT remains unclear. In the present study, we demonstrate that IL-1β caused activation of p38 mitogen-activated protein kinase and that the p38 inhibitor SB203580 significantly blocked the effect of IL-1β on INMDA-OUT in hippocampal CA1 neurons. Furthermore, the intracellular perfusion of active recombinant p38α significantly decreased the mean amplitude of INMDA-OUT. In neurons prepared from inflamed hippocampus, the mean amplitude of INMDA-OUT was significantly reduced. In the inflamed hippocampus, IL-1β and IL-1RI were expressed mainly in microglia and neurons, respectively. These results suggest that IL-1β increases the excitability of hippocampal CA1 neurons in the p38-dependent inhibition of INMDA-OUT.

【 授权许可】

Unknown