Experimental Febrile Seizures Impair Interastrocytic Gap Junction Coupling in Juvenile Mice
Experimental Febrile Seizures Impair Interastrocytic Gap Junction Coupling in Juvenile Mice
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DOI：
10.1002/jnr.23726
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发表时间：
2016-09-01
影响因子：
4.2
通讯作者：
Bedner, Peter
中科院分区：
文献类型：
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作者：
Khan, Dilaware;Dupper, Alexander;Bedner, Peter
持续性和局灶性热性惊厥（FS）与颞叶癫痫（TLE）的发生有关，但其潜在机制和易感危险因素的作用仍知之甚少。使用红藻氨酸模型的TLE，我们以前提供了强有力的证据表明，中断星形胶质细胞间隙连接介导的细胞间通讯是一个至关重要的事件在癫痫发生。为了进一步阐明这一点，我们通过高温（HT）诱导未成熟小鼠癫痫发作，以研究FS对海马星形胶质细胞网络的影响。实验性FS诱导5天后，通过小鼠急性切片中的示踪剂扩散研究评估了胞间偶联的变化。结果表明，HT诱导的FS引起海马星形胶质细胞缝隙连接偶联的显着减少超过50%。蛋白质印迹分析表明，减少连接蛋白43蛋白表达和/或磷酸化状态的变化占这种星形胶质细胞功能障碍。值得注意的是，解偶联发生在没有神经元死亡和反应性神经胶质增生的情况下。这些数据提供了FS和TLE的后续发展之间的机制联系，并进一步加强了星形胶质细胞在这种疾病的发病机制中发挥核心作用的新观点。(C)2016 Wiley Periodicals，Inc.
Prolonged and focal febrile seizures (FSs) have been associated with the development of temporal lobe epilepsy (TLE), although the underlying mechanism and the contribution of predisposing risk factors are still poorly understood. Using a kainate model of TLE, we previously provided strong evidence that interruption of astrocyte gap junction-mediated intercellular communication represents a crucial event in epileptogenesis. To elucidate this aspect further, we induced seizures in immature mice by hyperthermia (HT) to study the consequences of FSs on the hippocampal astrocytic network. Changes in interastrocytic coupling were assessed by tracer diffusion studies in acute slices from mice 5 days after experimental FS induction. The results reveal that HT-induced FSs cause a pronounced reduction of astrocyte gap junctional coupling in the hippocampus by more than 50%. Western blot analysis indicated that reduced connexin43 protein expression and/or changes in the phosphorylation status account for this astrocyte dysfunction. Remarkably, uncoupling occurred in the absence of neuronal death and reactive gliosis. These data provide a mechanistic link between FSs and the subsequent development of TLE and further strengthen the emerging view that astrocytes have a central role in the pathogenesis of this disorder. (C) 2016 Wiley Periodicals, Inc.