• Top page
  • Timetable
  • Per session
  • Per presentation
  • How to
  • Meeting Planner



Epilepsy, Headache, Vertigo

開催日 2014/9/11
時間 16:00 - 17:00
会場 Poster / Exhibition(Event Hall B)

Brain region-specific roles of glial glutamate transporter GLT1

  • P1-350
  • 杉本 潤哉 / Junya Sugimoto:1 伊藤 亨子 / Yukiko Itou:1 相馬 美歩 / Miho Soma:1 崔 万鵬 / Wanpeng Cui:1 三谷 章 / Akira Mitani:2 野村 政壽 / Masatoshi Nomura:3 高柳 涼一 / Ryoichi Takayanagi:3 相澤 秀紀 / Hidenori Aizawa:1 田中 光一 / Kohichi Tanaka:1,4,5 
  • 1:東医歯大難治疾患研分子神経科学 / Laboratory of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental Univ, Tokyo, Japan. 2:京都大院医人間健康 / Human Health Science, Graduate School of Medicine, Kyoto Univ, Kyoto, Japan. 3:九州大院医病態制御内科学 / Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu Univ, Fukuoka, Japan 4:東医歯大脳統合機能研セ / The Center for Brain Integration Research, Tokyo Medical and Dental Univ, Tokyo, Japan. 5:科学技術振興機構 CREST / JST CREST, Saitama, Japan. 

Glutamate excitotoxicity has been implicated as the common mechanism underlying neuropsychiartric disorders including epilepsy, schizophrenia, autism, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).
Glial glutamate transporter GLT1 plays dominant role in regulating the extracellular glutamate level. The reduced expression of GLT1 has been implicated in brain regions that are damaged in these disorders. To clarify the relationship between excitotoxicity and pathogenesis of these diseases in vivo, we generated brain region-specific GLT1 knockout mice by crossing floxed-GLT1 mouse with Cre lines expressing Cre recombinase in dorsal-telencephalon or diencephalon and brain stem.
Cortex-specific GLT1 knockout pups show spontaneous motor startles followed by a tonic extension of the four limbs associated with running around two weeks of age. Furthermore, degeneration of cortical layer 2/3 neurons and hippocampal pyramidal neurons are observed in the mutants.
On the other hand, mice with deficiency of GLT1 in thalamus and brain stem exhibit lethal spontaneous seizure with no significant cell death. In addition, the mutants exhibit depression-like behaviors.
These results indicate that GLT1 dysfunction in diencephalon and brain stem is associated with spontaneous lethal epileptic seizure and depression-like behaviors, whereas GLT1 in cortex plays a critical role in preventing infantile epilepsy and protecting cortical layer 2/3 and hippocampal pyramidal neurons from excitotoxicity. These region-specific GLT1 KO mice will be useful for understanding the role of excitotoxicity in neuropsychiatric diseases.

Copyright © Neuroscience2014. All Right Reserved.