Epileptogenesis-Associated Alterations of Heat Shock Protein 70 in a Rat Post-Status Epilepticus Model
Epileptogenesis-Associated Alterations of Heat Shock Protein 70 in a Rat Post-Status Epilepticus Model
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DOI：
10.1016/j.neuroscience.2019.06.031
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发表时间：
2019-09-01
期刊：
影响因子：
3.3
通讯作者：
Potschka, Heidrun
中科院分区：
文献类型：
--
作者：
Gualtieri, Fabio;Nowakowska, Marta;Potschka, Heidrun
颞叶癫痫是由最初的侮辱引发的，例如癫痫持续状态，这启动了癫痫的发展过程。热休克蛋白70(Hsp70)是一种普遍表达的分子伴侣，参与癫痫持续状态后上调的炎症反应。HSP70被认为是Toll样受体4的内源性细胞内配体，在炎症事件发生后由受损或坏死的组织和激活的免疫细胞释放。到目前为止，HSP70表达的时程和模式还没有详细的描述。因此，我们研究了癫痫持续状态大鼠颞叶癫痫模型中HSP70在海马区、海马区、顶叶区、杏仁核和丘脑的免疫组织化学表达。癫痫持续状态对Hsp70表达的影响在致痫后不同阶段有所不同，在致痫后早期作用较强，潜伏期作用较弱，慢性期作用不明显。细胞水平分析显示，Hsp70与神经元标志物Neun和Toll样受体4共定位，未发现与星形胶质细胞标志物GFAP或小胶质细胞标志物LBA1共定位。因此，针对癫痫发生的多靶向策略的发展应考虑致痫后早期Hsp70的调节作用。(C)2019年提交人(S)。爱思唯尔有限公司代表IBRO出版。
Temporal lobe epilepsy is triggered by an initial insult, such as status epilepticus, that initiates the process of epilepsy development. Heat shock protein 70 (Hsp70) is a ubiquitously expressed molecular chaperone, involved in the inflammatory response that is upregulated after status epilepticus. Hsp70 has been described as an endogenous intracellular ligand of Toll-like receptor 4. It is released from damaged or necrotic tissue and by activated immune cells after an inflammatory event. So far, the time course and the pattern of epileptogenesis-associated alterations in Hsp70 expression have not been described in detail.Thus, we investigated immunohistochemical expression of Hsp70 in hippocampus, parahippocampal cortex, parietal cortex, amygdala, and thalamus following status epilepticus in a rat model of temporal lobe epilepsy. The impact of status epilepticus on Hsp70 expression varied during different phases of epileptogenesis, displaying a stronger effect in the early post-insult phase, a milder and more localized effect in the latency phase and no relevant effect in the chronic phase.Cellular-level characterization revealed that Hsp70 colocalized with the neuronal marker NeuN and with Toll-like receptor 4. No colocalization with the astrocytic marker GFAP or the microglia marker lba1 was found.The intense neuronal Hsp70 upregulation during the early postinsult phase might contribute to the onset of excessive inflammation triggering molecular and cellular reorganization and generation of a hyperexcitable epileptic network. Therefore, development of multi-targeting strategies aiming at prevention of epileptogenesis should consider Hsp70 modulation in the early days following an epileptogenic insult. (C) 2019 The Author(s). Published by Elsevier Ltd on behalf of IBRO.