Association of Microtubule Dynamics with Chronic Epilepsy
Association of Microtubule Dynamics with Chronic Epilepsy
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DOI：
10.1007/s12035-015-9431-8
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发表时间：
2015-09
影响因子：
5.1
通讯作者：
Xin Xu;Yida Hu;Y. Xiong;Zhonggui Li;Wei Wang;Chao Du;Yong Yang;Yanke Zhang;F. Xiao;Xuefeng Wang
中科院分区：
文献类型：
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作者：
Xin Xu;Yida Hu;Y. Xiong;Zhonggui Li;Wei Wang;Chao Du;Yong Yang;Yanke Zhang;F. Xiao;Xuefeng Wang
大约30%的癫痫病例通过未知的机制对当前的药物治疗是难治的。关于突触成分在癫痫发病机制中的作用已经做了很多工作，但相对较少关注微管的潜在作用。本研究观察了30例人类癫痫组织和两种不同慢性癫痫大鼠模型的微管动力学水平。微管调节剂的管理减缓了慢性癫痫的进展。相反，微管解聚剂加重了慢性癫痫的进展。采用全细胞钳夹电生理指标观察微管调节剂和微管解聚剂对脑片神经元兴奋性和抑制性突触传递的影响。有趣的是，我们发现微管调节剂显著增加了中间神经元动作电位放电的频率，并显著提高了微型抑制性突触后电流的幅度和频率。微管解聚剂则有相反的作用。这些结果表明，调节高动力微管可能通过突触后机制在中间神经元中发挥抗癫痫作用。它可能代表癫痫治疗的潜在药理学靶点。
Approximately 30 % of epilepsy cases are refractory to current pharmacological treatments through unknown mechanisms. Much work has been done on the role of synaptic components in the pathogenesis of epilepsy, but relatively little attention has been given to the potential role of the microtubules. We investigated the level of microtubule dynamic in 30 human epileptic tissues and two different chronic epilepsy rat models. The administration of microtubule-modulating agent attenuated the progression of chronic epilepsy. By contrast, microtubule-depolymerizing agent aggravated the progression of chronic epilepsy. The electrophysiological index by whole-cell clamp was used to investigate the neuronal excitation and inhibitory synaptic transmission in brain slices after administration of microtubule-modulating agent and microtubule-depolymerizing agent. Interestingly, we found that microtubule-modulating agent significantly increased the frequency of action potential firing in interneurons, and significantly promoted the amplitudes and frequencies of miniature inhibitory postsynaptic currents. Microtubule-depolymerizing agent had an opposite effect. These findings suggest that modulating hyperdynamic microtubules may take an anti-epileptic effect via postsynaptic mechanisms in interneurons. It could represent a potential pharmacologic target in epilepsy treatment.