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Role of gap junctions in epilepsy

缝隙连接在癫痫中的作用

Abstract

Epilepsy is a common neurological disorder characterized by periodic and unpredictable seizures. Gap junctions have recently been proposed to be involved in the generation, synchronization and maintenance of seizure events. The present review mainly summarizes recent reports concerning the contribution of gap junctions to the pathophysiology of epilepsy, together with the regulation of connexin after clinical and experimental seizure activity. The anticonvulsant effects of gap junction blockers both in vitro and in vivo suggest that the gap junction is a candidate target for the development of antiepileptic drugs. It is also of interest that the roles of neuronal and astrocytic gap junctions in epilepsy have been investigated independently, based on evidence from pharmacological manipulations and connexin-knockout mice. Further studies using more specific manipulations of gap junctions in different cell types and in human epileptic tissue are needed to fully uncover the role of gap junctions in epilepsy.

摘要

癫痫是最常见的神经系统疾病之一, 临床主要表现为周期性和无法预见性的癫痫样发作。目前认为, 癫痫的形成、同步化以及癫痫样放电的维持与细胞间的缝隙连接有关。大量的体内外实验研究表明, 缝隙连接抑制剂具有较强的抗癫痫作用, 提示缝隙连接可能成为开发新型抗癫痫药物的潜在靶点。此外, 选择性药理学研究和基因敲除技术研究表明, 神经元间与胶质细胞间的缝隙连接在癫痫中的作用需区别看待。随着条件性基因敲除技术的成熟、高选择性的新型缝隙连接调控药物的出现以及更详细的人类癫痫脑组织样本的研究, 人们将更全面地了解缝隙连接在癫痫中的作用。本综述总结了目前关于缝隙连接在癫痫发病机制中作用的研究结果, 并对临床和基础研究中癫痫发作导致的缝隙连接蛋白表达的变化进行讨论。

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Correspondence to Chen Zhong.

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Jin, MM., Zhong, C. Role of gap junctions in epilepsy. Neurosci. Bull. 27, 389–406 (2011). https://doi.org/10.1007/s12264-011-1944-1

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Keywords

  • epilepsy
  • gap junction
  • connexin

关键词

  • 癫痫
  • 缝隙连接
  • 缝隙连接蛋白