title: Tubulin β-III modulates seizure activity in epilepsy.
abstract: Tubulin β-III (TUBB3) is the most dynamic β-tubulin isoform expressed in neurons, and is highly expressed in the central nervous system. However, the relationship between TUBB3 and epileptic seizures has not been thoroughly investigated. The aims of this study were to investigate the expression of TUBB3 in patients with temporal lobe epilepsy and two different rat models of chronic epilepsy, and to determine the specific roles of TUBB3 in epilepsy. TUBB3 expression was upregulated in human and rat epileptic tissue. Moreover, TUBB3 expression was associated with inhibitory GABAergic neurons and the inhibitory postsynaptic scaffold protein gephyrin. TUBB3 downregulation attenuated the behavioural phenotypes of epileptic seizures during the pilocarpine-induced chronic phase of epileptic seizures and the pentylenetetrazole kindling process, whereas TUBB3 overexpression had the opposite effect. Whole-cell clamp recordings and western blotting revealed that the amplitude of GABA-A receptor-mediated miniature inhibitory postsynaptic currents and the surface expression of the GABA-A receptor were increased in rats in which TUBB3 expression was downregulated. Importantly, TUBB3 interacted with GABA-A receptor-associated protein, which is known to be involved in GABA-A receptor trafficking. These results indicate that TUBB3 plays a critical role in the regulation of epileptic seizures via GABA-A receptor trafficking, suggesting a molecular mechanism for new therapeutic strategies. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, PR China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Shangguan
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, PR China.
authors.forename: Wei
authors.identifier: 0000-0002-8766-4760
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Du
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, PR China.
authors.forename: Yida
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Changlong
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, PR China.
authors.forename: Yanke
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, PR China.|Centre of Epilepsy, Beijing Institute for Brain Disorders, Beijing, PR China.
authors.forename: Xuefeng
authors.identifier: 0000-0002-8477-7380
authors.initials: X
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D015536:Down-Regulation / Q000502:physiology; D004569:Electroencephalography; D005260:Female; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D018020:Lithium Compounds / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D018721:Muscarinic Agonists / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D012640:Seizures / Q000503:physiopathology*; D014404:Tubulin / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology; D055815:Young Adult
chemical_list: D018020:Lithium Compounds; D018721:Muscarinic Agonists; C498585:TUBB3 protein, human; D014404:Tubulin; D010862:Pilocarpine
keywords: GABA; GABARAP; TUBB3; epileptic seizures