塗谷 睦生 (ヌリヤ ムツオ)

Nuriya, Mutsuo

写真a

所属(所属キャンパス)

医学部 薬理学教室 (信濃町)

職名

准教授

HP

経歴 【 表示 / 非表示

  • 2004年10月
    -
    2007年03月

    Columbia University / Howard Hughes Medical Institute, 博士研究員

  • 2007年04月
    -
    継続中

    慶應義塾大学, 医学部薬理学教室, 専任講師

  • 2012年04月
    -
    継続中

    横浜国立大学, 環境情報学府, 客員准教授

  • 2016年12月
    -
    継続中

    慶應義塾大学, 医学部薬理学教室, 准教授

学歴 【 表示 / 非表示

  •  

    東京大学, 理学部, 生物化学科

    日本, 大学, 卒業

  •  

    The Johns Hopkins University, School of Medicine, Department of Neuroscience

    U.S.A., 大学院, 修了, 博士

学位 【 表示 / 非表示

  • Ph.D., The Johns Hopkins University, 2004年

 
 

論文 【 表示 / 非表示

  • Norepinephrine induces rapid and long-lasting phosphorylation and redistribution of connexin 43 in cortical astrocytes

    塗谷 睦生

    Biochemical and Biophysical Research Communications (Biochemical and Biophysical Research Communications)  504 ( 4 ) 690 - 697 2018年10月

    研究論文(学術雑誌),  ISSN  0006-291X

     概要を見る

    © 2018 Elsevier Inc. Norepinephrine (NE) modulates brain functions depending on both the internal and external environment. While the neuromodulatory actions of NE have been well characterized, the response and involvement of cortical astrocytes to physiological noradrenergic systems remain largely unknown, especially at the molecular level. In this study, we biochemically characterize the action of NE on astrocytes of the murine neocortex. NE stimulation of acute brain slices rapidly increase phosphorylation of connexin 43 (Cx43) at Serine (Ser) 368, in slices from both juvenile and adolescent animals. The phosphorylation is mediated by the protein kinase C (PKC) pathway under the α1-adrenergic receptor and remains elevated for tens of minutes following brief exposure to NE, well after the intracellular calcium level returns to normal level, suggesting the plastic nature of this phosphorylation event. Importantly, this phosphorylation event persists in the absence of neuronal transmissions, suggesting that the effect of NE on Cx43 phosphorylation is induced directly on astrocytes. Furthermore, these NE-induced phosphorylations are associated with biochemical dissociation of Cx43 from gap-junctional plaques to non-junctional compartments. Finally, we show that pharmacological manipulation of the noradrenergic system using psychoactive drugs modulates phosphorylation of Cx43 in the cerebral cortex in vivo. These data suggest that NE acts directly on astrocytes in parallel with neurons and modulates functionally critical connexin channel proteins in a plastic manner. Thus, plasticity of astrocytes induced by the “gliomodulatory” actions of NE may play important roles in their physiological as well as pharmacological actions in the brain.

  • Direct posttranslational modification of astrocytic connexin 43 proteins by the general anesthetic propofol in the cerebral cortex

    塗谷 睦生

    Biochemical and Biophysical Research Communications (Biochemical and Biophysical Research Communications)  497 ( 2 ) 734 - 741 2018年03月

    研究論文(学術雑誌),  ISSN  0006-291X

     概要を見る

    © 2018 Elsevier Inc. Propofol is widely used as a general anesthetic and is generally considered to exert its action by regulating neuronal firing via facilitation of GABAA receptors. However, accumulating evidence suggests that propofol also acts on astrocytes, including inhibitory effects on gap junctional coupling, but the underlying molecular mechanisms remain largely unknown. Here, using acute cortical brain slices prepared from mice, we characterize propofol-induced molecular changes in astrocytic gap junction protein connexin 43 (Cx43). Propofol does not change the protein expression level of Cx43 or its incorporation into gap junctional plaques, according to biochemical and immunohistochemical analyses. However, propofol alters migration pattern of Cx43 on western blot, suggesting changes in its posttranslational modifications. Indeed, this change is accompanied by an increase in the phosphorylation of Cx43 at serine 368, which is known to reduce permeability of Cx43 gap junctions. Finally, we show that this change occurs in the absence of neuronal firing or glutamatergic transmissions. Overall, these results show that propofol induces posttranslational modification of Cx43 directly on astrocytes at the site of gap junctional plaques, exerting direct pharmacological action on astrocytes in parallel with its action on neurons.

  • Background norepinephrine primes astrocytic calcium responses to subsequent norepinephrine stimuli in the cerebral cortex

    塗谷 睦生

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 483 ( 1 ) 732 - 738 2017年01月

    研究論文(学術雑誌),  ISSN  0006-291X

  • Multimodal two-photon imaging using a second harmonic generation-specific dye

    塗谷 睦生

    NATURE COMMUNICATIONS 7   732 - 738 2016年05月

    研究論文(学術雑誌),  ISSN  2041-1723

  • Astrovascular interaction

    Nuriya Mutsuo

    Folia Pharmacologica Japonica 145 ( 6 ) 326 - 328 2015年06月

    ISSN  0015-5691

全件表示 >>

KOARA(リポジトリ)収録論文等 【 表示 / 非表示

競争的資金等の研究課題 【 表示 / 非表示

  • アストロサイトの構造機能連関とその制御の解明

    2016年04月
    -
    2019年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 塗谷 睦生, 基盤研究(C), 補助金,  代表

  • SHG専用色素を用いたマルチモダル2光子顕微鏡の開発と応用

    2016年04月
    -
    2018年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 塗谷 睦生, 新学術領域研究(研究領域提案型), 補助金,  代表

 

担当授業科目 【 表示 / 非表示

  • 薬理学

    2019年度

担当経験のある授業科目 【 表示 / 非表示

  • MCB-I

    慶應義塾, 2015年度

  • 基礎分子細胞学

    慶應義塾, 2015年度

  • 薬理学

    慶應義塾, 2015年度