Delayed activation and modulation of p38 MAPKs in the brain of mice following KA-induced seizure

초록

p38 MAPK has been implicated in pathological changes in the course of inflammatory and apoptotic processes in various cell types including neurons. Here we report the delayed activation of p38 MAPK in adult mouse brain following seizures induced by systemic administration of kainic acid (KA). Immunoreactivity of both p38 and p38 MAPKs was markedly increased in the brain 4 days after KA administration in the areas undergoing severe neuronal degeneration. In particular, the immunoreactivity for p38 was dramatically increased in astroglial cells in CA3 and CA1 regions of hippocampus with an enriched localization in nucleus. Such an increased expression of p38 MAPK in glia was sustained for up to 10 days after the KA-treatment. The induction of p38 in the hippocampus of seizure-experienced animals was repressed to the level seen in control animals by pre-administration of a selective nNOS inhibitor, 7-nitroindazole (7-NI), and such a repression was reversed by the co-injection of L-Arginine, the substrate of NOS. The delayed and protracted activation of p38 MAPK in astrocytes in the brain of animals with status epilepticus raise a possibility for the role of p38 MAPK signal pathway in delayed neuronal death and/or reactive gliosis that might be modulated by NO produced by nNOS.