Delayed induction of p38 MAPKs in reactive astrocytes in the brain of mice after KA-induced seizure
Delayed induction of p38 MAPKs in reactive astrocytes in the brain of mice after KA-induced seizure
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DOI：
10.1016/s0169-328x(01)00233-9
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发表时间：
2001-10-19
期刊：
影响因子：
--
通讯作者：
Lee, JK
中科院分区：
文献类型：
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作者：
Che, YZ;Yu, YM;Lee, JK
p38丝裂原活化蛋白激酶（p38 MAPK）的激活与包括神经元在内的各种细胞类型的炎症和凋亡过程的病理变化有关。在这里，我们报道了kainic酸（KA）诱导的癫痫发作后小鼠大脑中p38 MAPKs的延迟诱导。KA给药4天后，大脑中p38 α和p38 β MAPKs的免疫反应活性显著增加，特别是在选择性神经元丢失的区域。特别是p38 β在海马CA3和CAI区的反应性星形胶质细胞中显著升高，其在星形胶质细胞核中的定位丰富。ka处理后p38 β的诱导持续10天以上。选择性神经元一氧化氮合酶（nNOS）抑制剂7-硝基茚唑（7-NI）可抑制癫痫发作动物海马神经元延迟死亡和星形胶质细胞形成，并显著抑制星形胶质细胞p38 β MAPK的延迟诱导。与NOS底物l -精氨酸（L-arg）共注射可逆转这种抑制，同时神经元死亡加重。综上所述，这些数据表明p38 MAPK信号通路在ka诱导癫痫小鼠的延迟神经元死亡和/或反应性胶质瘤中起作用。(C) 2001 Elsevier Science版权所有
Activation of p38 mitogen-activated protein kinase (p38 MAPK) has been implicated in pathological changes in inflammatory and apoptotic processes in various cell types including neurons. Here we report the delayed induction of p38 MAPKs in the brain of mice following kainic acid (KA)-induced seizure. The immunoreactivities of p38 alpha and p38 beta MAPKs were markedly increased in the brain 4 days after KA administration, especially in the areas undergoing selective neuronal loss. In particular, p38 beta was dramatically increased in reactive astrocytes of CA3 and CAI regions of hippocampus with its enriched localization in the nucleus of astrocytes. The induction of p38 beta was sustained for more than 10 days after KA-treatment. Pre-administration of the selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI), which suppressed the delayed neuronal death as well as astrogliosis in hippocampus of seizure-experienced animals, dramatically repressed the delayed induction of p38 beta MAPK in astrocytes. The repression was reversed by the co-injection with L-arginine, (L-arg), a substrate for NOS, which coincided with the aggravation of neuronal death. Together, these data suggested a role of p38 MAPK signal pathway in delayed neuronal death and/or in reactive gliosis in mice with KA-induced seizure. (C) 2001 Elsevier Science BY All rights reserved.