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Working Memory and Executive Function

開催日 2014/9/13
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Prefrontal cortex-specific deletion of glial glutamate transporter GLT-1 causes behavioral changes relevant to schizophrenia in mice

  • P3-233
  • 橋本 真理子 / Mariko Hashimoto:1 相澤 秀紀 / Hidenori Aizawa:1 相田 知海 / Tomomi Aida:1 崔 万鵬 / Wanpeng Cui:1 水上 浩明 / Hiroaki Mizukami:2 小澤 敬也 / Kinya Ozawa:2 野村 政壽 / Masatoshi Nomura:3 高柳 涼一 / Ryuichi Takayanagi:3 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 / Lab of Mol Neurosci, Med Res Inst, Tokyo Med Dent Univ, Tokyo, Japan 2:自治医大遺伝子治療研究部 / Div of Genet Therapeutics, Cent Mo Med, Jichi Med Univ, Tochigi, Japan 3:九州大医病態制御内科学分野 / Dept of Med Bioreg, Grad Sch Med Sci, Kyushu Univ, Fukuoka, Japan 4:科学技術振興機構 / JST, CREST, Saitama, Japan 5:東医歯大脳統合機能研セ / Cent Brain Int Res, Tokyo Med Dent Univ, Tokyo, Japan 

Schizophrenia patients carrying a common single nucleotide polymorphism in glial glutamate transporter GLT-1, which leads to reduced expression of GLT-1, are reported to show poor performance of working memory task, one of the cognitive symptoms of schizophrenia. Despite a primary role of GLT-1 in clearance of extracellular glutamate, the etiologic role of GLT-1 for cognitive dysfunctions in schizophrenia remains unclear. Since medial prefrontal cortex (mPFC) is essential region for working memory, we hypothesized that impairment of GLT-1 activity in mPFC causes behavioral changes relevant to the cognitive dysfunction in schizophrenia. To address this, mPFC-specific GLT-1 conditional knockout (cKO) was generated by injecting adeno-associated virus expressing Cre into mPFC of floxed GLT-1 mice. We observed the significant reduction of GLT-1 protein in mPFC of GLT-1 cKO four weeks after injection. Behavioral analyses revealed that mPFC-specific GLT-1 cKO mice specifically showed the impairment of spontaneous alternation in Y-maze test and pre-pulse inhibition in startle response test. These results suggested that reduction of GLT-1 activity in mPFC caused cognitive dysfunction relevant to the schizophrenia, such as deficits in working memory and sensorimotor gating.

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