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Novel regulatory mechanism of anesthetic efficay by GABA-A receptor trafficking

Research Project

Project/Area Number 15K10503
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Anesthesiology
Research InstitutionHirosaki University

Principal Investigator

UENO Shinya  弘前大学, 医学研究科, 教授 (00312158)

Co-Investigator(Kenkyū-buntansha) 尾崎 拓  弘前大学, 医学研究科, 特任助教 (70621069)
Research Collaborator FURUKAWA Tomonori  弘前大学, 大学院医学研究科, 助教 (60402369)
NIKAIDOU Yoshikazu  弘前大学, 大学院医学研究科, 助教 (50613478)
SHIMOYAMA Shuji  弘前大学, 大学院医学研究科, 助教 (60736370)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords麻酔作用調節 / GABA-A受容体トラフィッキング / 受容体リン酸化調節 / 麻酔薬 / GABA / 受容体トラフィッキング / 受容体リン酸化 / GABA-A受容体細胞内分布 / シナプス外GABA-A受容体 / ベンゾジアゼピン長期投与
Outline of Final Research Achievements

We showed that efficacy of anesthetics was regulated by GABA-A receptor trafficking via receptor phosphorylation. GABA-A receptor is the major target protein of anesthetics and distributed synaptic and extrasynaptic sites of plasma membrane. Disruption of trafficking of these receptors from synaptic to extrasynaptic sites caused to reduce the efficacy of anesthetics. Interesingly, this reduced effect was rescued in the presence of dephosphorylation inhibitor. These results indicated that the levels of phosphorylation in the receptor determined the efficacy of anesthetics, suggesting that efficacy of anesthetics is controlable even after administration of anesthetics.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (23 results)

All 2018 2017 2016 2015

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 10 results,  Acknowledgement Compliant: 5 results) Presentation (13 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Morphological dendritic spine changes of medium spiny neurons in the nucleus accumbens in 6-hydroxydopamine-lesioned rats treated with levodopa.2017

    • Author(s)
      Funamizu Y, Nishijima H, Ueno T, Ueno S, Mizukami H, Yagihashi S, Tomiyama M.
    • Journal Title

      Neurosci Res.

      Volume: 121 Pages: 49-53

    • DOI

      10.1016/j.neures.2017.03.010

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Levodopa treatment and dendritic spine pathology.2017

    • Author(s)
      Nishijima H, Ueno T, Funamizu Y, Ueno S, Tomiyama M.
    • Journal Title

      Mov Disord.

      Volume: 印刷中 Issue: 6 Pages: 877-888

    • DOI

      10.1002/mds.27172

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Propofol anesthesia is reduced in Phospholipase C-related inactive protein type-1 knockout mice2017

    • Author(s)
      Nikaido Y, Furukawa T, Shimoyama S, Yamada J, Migita K, Koga K, Kushikata T, Hirota K, Kanematsu T, Hirata M, Ueno S
    • Journal Title

      The Journal of pharmacology and experimental therapeutics

      Volume: 361(3) Issue: 3 Pages: 367-374

    • DOI

      10.1124/jpet.116.239145

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic diazepam administration increases the expression of Lcn2 in the CNS2017

    • Author(s)
      Tomonori Furukawa, Shuji Shimoyama, Yasuo Miki, Yoshikazu Nikaido, Kohei Koga, Kazuhiko Nakamura, Koichi Wakabayashi & Shinya Ueno
    • Journal Title

      Pharmacology Research & Perspectives

      Volume: 5(1) Issue: 1 Pages: 1-12

    • DOI

      10.1002/prp2.283

    • NAID

      120006576912

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activations of muscarinic M1 receptors in the anterior cingulate cortex contribute to the antinociceptive effect via GABAergic transmission2017

    • Author(s)
      Kohei Koga, Yu Matsuzaki, Kenji Honda, Fumihiro Eto, Tomonori Furukawa, Keisuke Migita, Keiichi Irie, Kenichi Mishima and Shinya Ueno
    • Journal Title

      Molecular Pain

      Volume: 13 Pages: 1-11

    • DOI

      10.1177/1744806917692330

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Spine enlargement of pyramidal tract-type neurons in the motor cortex of a rat model of levodopa-induced dyskinesia2017

    • Author(s)
      Tatsuya Ueno, Haruo Nishijima, Shinya Ueno and Masahiko Tomiyama
    • Journal Title

      Frontiers in Neuroscience

      Volume: 11 Pages: 206-206

    • DOI

      10.3389/fnins.2017.00206

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Duloxetine increases the effects of levodopa in a rat model of Parkinson’s disease2016

    • Author(s)
      Haruo Nishijima, Tatsuya Ueno, Shinya Ueno and Masahiko Tomiyama
    • Journal Title

      Neurology and Clinical Neurosci

      Volume: 4 Issue: 4 Pages: 129-133

    • DOI

      10.1111/ncn3.12051

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] HSP90 Regulation of P2X7 Receptor Function Requires an Intact Cytoplasmic C-Terminus.2016

    • Author(s)
      Migita K, Ozaki T, Shimoyama S, Yamada J., Nikaido Y, Furukawa T, Shiba Y, Egan TM, Ueno S.
    • Journal Title

      Molecular Pharmacology

      Volume: 90 (2) Issue: 2 Pages: 116-126

    • DOI

      10.1124/mol.115.102988

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] cis-3-Hexenol and trans-2-hexenal mixture prevents development of PTSD-like phenotype in rats.2016

    • Author(s)
      Yoshikazu Nikaido, Junko Yamada, Keisuke Migita, Yuko Shiba, Tomonori Furukawa, Toshihiro Nakashima, Shinya Ueno
    • Journal Title

      Behavioural brain research

      Volume: 297 Pages: 251-258

    • DOI

      10.1016/j.bbr.2015.10.023

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Spontaneous epileptic seizures in transgenic rats harboring a human ADNFLE missense mutation in the β2-subunit of the nicotinic acetylcholine receptor.2015

    • Author(s)
      Yuko Shiba, Fumiaki Mori, Junko Yamada, Keisuke Migita, Yoshikazu Nikaido, Koichi Wakabayashi, Sunao Kaneko, Motohiro Okada, Shinichi Hirose, Shinya Ueno
    • Journal Title

      Neuroscience research

      Volume: 100 Pages: 46-54

    • DOI

      10.1016/j.neures.2015.06.003

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] The effect of chronic diazepam administration on hippocampal long-term potentiation and spine morphology2018

    • Author(s)
      Tomonori Furukawa, Yoshikazu Nikaido, Shuji Shimoyama, Yoshiki Ogata, Kazuhiko Nakamura and Shinya Ueno
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The Association Between Anxiety and Motor Function Recovery After Spinal Cord Injury In Gabaa Receptor-defective Mice2018

    • Author(s)
      TAKU FUJITA; Gentaro Kumagai; Xizhe Liu; Hitoshi Kudo; Toru Asari; Yoshikazu Nikaido; Shinya Ueno; Yasuyuki Ishibashi
    • Organizer
      ORS 2018 Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Chronic diazepam administration increases the expression of Lcn2 in the CNS2017

    • Author(s)
      Tomonori Furukawa, Shuji Shimoyama, Yasuo Miki, Yoshikazu Nikaido, Kohei Koga, Kazuhiko Nakamura, Koichi Wakabayashi, and Shinya Ueno
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      アクトシティ浜松(浜松市)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] Chronic diazepam administration impairs acquisition of spatial reference memory in aged mice2017

    • Author(s)
      Yoshikazu Nikaido, Tomonori Furukawa, Shuji Shimoyam, Kohei Koga, and Shinya Ueno
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      アクトシティ浜松(浜松市)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] The effect of chronic diazepam administration on Lcn2 expression and spine morphology2017

    • Author(s)
      Tomonori Furukawa, Shuji Shimoyama, Yoshikazu Nikaido, Yasuo Miki, Kohei Koga, Kazuhiko Nakamura, Koichi Wakabayashi, and Shinya Ueno
    • Organizer
      第40回神経科学学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] AP-1 complex induces mouse Tspo gene expression by lipopolysaccharide in microglial cell line, BV-22017

    • Author(s)
      Shuji Shimoyama, Tomonori Furukawa, Yoshiki Ogata, Shinya Ueno and Kazuhiko Nakamura
    • Organizer
      第44回日本脳科学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The effect of chronic diazepam administration induced upregulation of Lcn2 expression on cognitive function2017

    • Author(s)
      Yoshiki Ogata, Tomonori Furukawa, Yoshikazu Nikaido, Shuji Shimoyama, Kazuhiko Nakamura and Shinya Ueno
    • Organizer
      第44回日本脳科学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Phospholipase C-related inactive protein type-1 deficiency alters anesthetic electroencephalogram induced by propofol in mice2017

    • Author(s)
      Yoshikazu Nikaido, Tomonori Furukawa, Shuji Shimoyama, Tetsuya Kushikata, Kazuyoshi Hirota, Takashi Kanematsu, Masato Hirata and Shinya Ueno
    • Organizer
      第40回神経科学学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 慢性社会的敗北ストレスによってうつ病様モデル化したラットは前頭前野の機能異常を起こす2017

    • Author(s)
      二階堂義和, 古川智範, 下山修司, 櫛方哲也, 廣田和美, 上野伸哉
    • Organizer
      第44回日本脳科学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 遺伝子Tspo の発現調節メカニズムの解明2016

    • Author(s)
      下山修司、中村和彦、上野伸哉
    • Organizer
      日本生化学会 東北支部 第82 回例会・シンポジウム
    • Place of Presentation
      弘前大学(弘前市)
    • Year and Date
      2016-05-21
    • Related Report
      2016 Research-status Report
  • [Presentation] 社会ストレスは認知脳低下を来す2016

    • Author(s)
      二階堂義, 古川智範, 古賀浩平, 上野伸哉
    • Organizer
      第93回 日本生理学会大会
    • Place of Presentation
      札幌コンベンションセンター(札幌市)
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report
  • [Presentation] ラット前帯状皮質は恐怖記憶の想起と消去では左右異なる活動を示す2016

    • Author(s)
      古川智範、二階堂義和、右田啓介、下山修司、尾崎拓、古賀浩平、上野伸哉
    • Organizer
      第93回 日本生理学会大会
    • Place of Presentation
      札幌コンベンションセンター(札幌市)
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report
  • [Presentation] 麻酔科医が知っておくべき中枢神経系受容体:GABA-A受容体トラフィッキングによる麻酔効果制御2015

    • Author(s)
      上野伸哉
    • Organizer
      日本麻酔学会 第62回学術集会
    • Place of Presentation
      神戸ポートピアホテル(神戸市)
    • Year and Date
      2015-05-28
    • Related Report
      2015 Research-status Report
    • Invited

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Published: 2015-04-16   Modified: 2019-03-29  

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