title: Association of Microtubule Dynamics with Chronic Epilepsy.
abstract: 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.
authors.affiliation: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yida
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Du
authors.affiliation: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yanke
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. xfyp@163.com.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002908:Chronic Disease; D004827:Epilepsy / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D019579:Neocortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009665:Noscapine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050257:Tubulin Modulators / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D050257:Tubulin Modulators; D009665:Noscapine
keywords: GABA; Interneuron; Microtubule dynamics; Temporal lobe epilepsy; Tyrosinated α-tubulin