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Synaptic Plasticity

開催日 2014/9/13
時間 17:10 - 18:10
会場 Room J(313+314)
Chairperson(s) 竹本 さやか / Sayaka Takemoto-Kimu (東京大学大学院医学系研究科 神経生化学教室 / Department of Neurochemistry, Graduate School of Medicine, University of Tokyo, Japan)
安部 健太郎 / Kentaro Abe (京都大学大学院医学研究科 生体情報科学講座 / Department of Biological Sciences, Graduate School of Medecine, Kyoto University, Japan)

Functional analysis of protein tyrosine phosphatase Shp2 in the adult forebrain neurons

  • O3-J-5-2
  • 大西 浩史 / Hiroshi Ohnishi:1 草苅 伸也 / Shinya Kusakari:2 齋藤 文仁 / Fumihito Saitow:3 橋本 美穂 / Miho Hashimoto:1 松崎 泰教 / Yasunori Matsuzaki:4 小谷 武徳 / Takenori Kotani:5 村田 陽二 / Yoji Murata:5 平井 宏和 / Hirokazu Hirai:4 鈴木 秀典 / Hidenori Suzuki:3 的崎 尚 / Takashi Matozaki:5 
  • 1:群馬大院・保健・生体情報 / Dept Lab Sci, Gunma Univ Grad Sch Health Sci, Gunma, Japan 2:群馬大・生体調節研・バイオシグナル / Lab Biosig Sci, Inst Mol Cell Reg, Gunma Univ, Gunma, Japan 3:日本医科大・医・薬理 / Dept Pharmacol, Nippon Med Sch, Tokyo, Japan 4:群馬大院・医・神経生理 / Dept Neurophysiol, Gunma Univ Grad Sch Med, Gunma, Japan 5:神戸大院・医・シグナル統合 / Div Mol Cell Signal, Dept Biochem Mol Biol, Kobe Univ Grad Sch Med, Kobe, Japan 

Shp2, Src homology 2 domain-containing protein tyrosine phosphatase 2, is crucial for cell growth and differentiation. However, Shp2 is also expressed in post-mitotic neurons, and mutations of Shp2 are associated with a clinical condition of mental retardation. To investigate the roles of Shp2 in the adult brain, we selectively deleted Shp2 gene in post-mitotic neurons in conditional knockout (cKO) mice that was obtained by crossing CaMKII-Cre transgenic mice with Shp2-floxed mice. Shp2 cKO mice showed normal brain structure but exhibited abnormal behaviors including hyperactivity. In the brain of Shp2 cKO mice, novelty-induced expression of immediate early genes was significantly attenuated, suggesting a reduction of neuronal excitability. Ablation of Shp2 significantly increased high K+-induced activation of MAPK in both cultured neurons and synaptosomes, while BDNF-induced activation of MAPK was significantly reduced in Shp2-knockdown neurons. We also found that the efficiency of synaptic transmission was reduced in the hippocampus of Shp2 cKO mice. In addition, post-tetanic potentiation and paired pulse facilitation were attenuated and enhanced, respectively, in the hippocampal slice prepared from Shp2 cKO mice. They also showed temporary impaired memory formation in Morris water maze. These data suggest that Shp2 participates in regulation of activation of MAPK and synaptic plasticity in post-mitotic forebrain neurons, and thus contributes to regulation of locomotor activity and memory formation.

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