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Spatiotemporal regulation of glutamate distribution by transporters (EAATs/VGLUTs) and implications in neuropsychiatric disorders

開催日 2014/9/13
時間 9:00 - 11:00
会場 Room E(301)
Chairperson(s) 田中 光一 / Kohichi Tanaka (東京医科歯科大学難治疾患研究所分子神経科学分野 / Medical Research Institute & CBIR, Tokyo Medical & Dental University, Japan)
木下 専 / Makoto Kinoshita (名古屋大学大学院理学研究科生命理学専攻 / Department of Molecular Biology, Nagoya University Graduate School of Science, Japan)

Glial glutamate transporter deficiency alteres neurotransmission, leading to excessive repetitive behaviours in mice

  • S3-E-1-2
  • 相田 知海 / Tomomi Aida:1 吉田 純一 / Junichi Yoshida:1 野村 政壽 / Masatoshi Nomura:2 谷村 あさみ / Asami Tanimura:3 飯野 祐介 / Yusuke Iino:1 相馬 美歩 / Miho Soma:1 Bai Ning / Ning Bai:1 伊藤 亨子 / Yukiko Ito:1 Cui Wangpeng / Wangpeng Cui:1 相澤 秀紀 / Hidenori Aizawa:1 永井 てるみ / Terumi Nagai:4 高田 則雄 / Norio Takata:4 髙栁 涼一 / Ryoichi Takayanagi:2 狩野 方伸 / Masanobu Kano:3 Magdalena Götz / Götz Magdalena:5 平瀬 肇 / Hajime Hirase:4 田中 光一 / Kohichi Tanaka:1,6,7 
  • 1:東京医科歯科大学 / Lab Mol Neurosci, Med Res Instit, Tokyo Medical and Dental Univ (TMDU), Japan 2:九州大院医病態制御内科 / Dept Med Bioregulatory Sci, Kyushu Univ, Fukuoka, Japan 3:東京大院医神経生理 / Dept Neurophysiol, Univ of Tokyo, Tokyo, Japan 4:理研BSI神経グリア回路 / Lab Neuron-Glia Circuitry, BSI, RIKEN, Saitama, Japan 5:Physiol Genomics, Inst Physiol, Ludwig-Maximilian Univ, Munich, Germany / Physiol Genomics, Inst Physiol, Ludwig-Maximilian Univ, Munich, Germany 6:東京医歯大脳統合機能研究セ / Center Brain Integrated Research (CBIR), TMDU, Tokyo, Japan 7:JST / JST, CREST, Saitama, Japan 

Brain hyperexcitability has been proposed to a cause series of neuropsychiatric disorders. It is controlled by neurons and astrocytes. In astrocytes, the glial glutamate transporters GLT1 and GLAST are responsible for regulating brain excitability. However, the role of glial glutamate transporters in the pathogenesis of neuropsychiatric disorders remains unknown. We show that GLT1 inducible knockout (GLASTCreERT2/+/GLT1flox/flox, iKO) mice developed severe facial skin lesions and exhibited pathologic repetitive behaviour such as self-grooming. Although the repetitive behaviour is the common core symptoms of autism, obsessive compulsive disorder (OCD) and Tourette's syndrome, iKO mice did not exhibit other autism- or OCD-like symptoms (anxiety and abnormal social behaviour), but rather exhibited other Tourette's syndrome-like tics. Seizure sensitivity and excitatory transmission at the corticostriatal synapses after repetitive stimulation were increased in iKO mice. Furthermore, administration of an N-methyl-D-aspartate (NMDA) receptor antagonist memantine suppressed the pathologic repetitive behaviours in iKO mice. These data suggest that iKO mice as a novel animal model for Tourette's syndrome and suppression of brain hyperexcitability by NMDA receptor blockade may be effective for Tourette's syndrome.

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