Mitogen-activated protein kinase is increased in the limbic structures of the rat brain during the early stages of status epilepticus
Mitogen-activated protein kinase is increased in the limbic structures of the rat brain during the early stages of status epilepticus
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DOI：
10.1016/s0361-9230(98)00075-6
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发表时间：
1998-10-01
影响因子：
3.8
通讯作者：
Naffah-Mazzacoratti, MG
中科院分区：
文献类型：
--
作者：
Garrido, YCS;Sanabria, ERG;Naffah-Mazzacoratti, MG
毛果芸香碱（PILO）全身给药在成年大鼠中产生急性边缘系统癫痫发作，导致癫痫持续状态。最近的研究表明，在实验诱导的癫痫发作过程中，有丝分裂原活化蛋白激酶（MAPK）级联反应被激活。本研究采用免疫细胞化学方法观察了PILO诱导的癫痫持续状态大鼠脑内MARK蛋白及其活性形式（A-MAPK）的时空分布。结果表明，正常和癫痫大鼠脑内MARK蛋白及其活性形式（A-MAPK）的分布不同。生理盐水处理的大鼠，以及动物接受PILO，但没有发展到癫痫持续状态，表现出弱，但选择性MAPK免疫反应，检测海马锥体神经元，齿状回，门，CA 3，CA 1，和内嗅，梨状，扣带皮质。A-MARK免疫反应，而不是只观察到在CA 3和门的神经突和内嗅和梨状皮质的细胞，在PILO治疗的大鼠，癫痫状态后30和60分钟之间，有增加的免疫反应，以两种抗体，这是不同的分布在整个边缘系统的几个结构。癫痫持续状态5 h后，MARK和A-MARK免疫阳性表达略有下降，12 h后，MARK和A-MARK免疫阳性表达明显下降，几乎恢复到基础表达水平。这些研究结果是一致的空间和时间依赖性的MAPK表达在选定的边缘结构，其激活可能代表一个初始触发神经元的修改，可能参与急性癫痫发生的机制，并在持久的神经病理学变化的PILO癫痫模型。(C)1998年爱思唯尔科学公司
Systemic administration of pilocarpine (PILO) in adult rat produces acute limbic seizures leading to states epilepticus. Recent studies have shown the activation of mitogen-activated protein kinase (MAPK) cascades during experimentally induced seizures. MAPK activation may be triggered by glutamatergic stimulation and may play a key role in signal transduction pathways, In the present study, immunocytochemistry was used to analyze the spatiotemporal distribution pattern of the MARK protein and its active form (A-MAPK) following PILO-induced status epilepticus, MAPK and A-MARK immunoreactivities exhibited different patterns of distribution in the brain of normal and epileptic rats. The saline-treated rats, as well as the animals that received PILO but did not evolve to status epilepticus, showed a weak but selective MAPK immunoreactivity, detected in the hippocampal pyramidal neurons, dentate gyrus, hilus, CA3, CA1, and entorhinal, piriform, and cingulate cortices. A-MARK immunoreactivity was instead observed only in neurites of the CA3 and hilus and in cells of the entorhinal and piriform cortices, In PILO-treated rats, between 30 and 60 min after states epilepticus there was an increase of the immunoreactivity to both antibodies, which were differently distributed throughout several structures of the limbic system. The immunostaining showed a slight decrease after 5 h of states epilepticus, However, MARK and A-MARK immunopositivities decreased markedly after 12 h of states epilepticus, returning almost to the basal expression. These findings are consistent with a spatial and time-dependent MAPK expression in selected limbic structures, and its activation could represent an initial trigger for neuronal modifications that may take part in the mechanism underlying acute epileptogenesis and in longlasting neuropathological changes of the PILO model of epilepsy. (C) 1998 Elsevier Science Inc.