SB203580 투여를 통한 KA에 의해 유도되는 신경세포 사멸 억제

초록

Activation of p38 MAPK has been implicated in pathological changes in inflammatory and apoptotic processes in various cell types including neurons. In previous report, we showed the delayed induction of p38 MAPKs in the brain of mice following kainic acid (KA)-induced seizure. Immunohistochemical study revealed the induction of p38 MAPKs in reactive astrocytes in CA3 region of hippocampus. Here we report the delayed and protracted induction of kinase activity of p38 MAPKs in CA3 region of hippocampus, where severe neuronal loss occurs after KA administration. We observed the induction of kinase activity of p38 MAPKs beginning 30 min after KA treatment, which was sustained until 4 days after KA treatment. In addition, we demonstrated that the inhibition of p38 MAPKs by SB203580, a p38 MAPK inhibitor, attenuates the neuronal loss in CA3 in the hippocampus, which was accompanied by the suppression of the p38 MAPKs activation as well as the astrogliosis. Together with the previous report on immunohistological localization of p38 MAPK in astrocytes, the results indicated that the delayed and sustained induction of p38 MAPK in activating astrocytes plays a crucial role in neuronal damage in KA-induced seizure brain.