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Studies on regulatory mechanisms of brain function by protein kinase C-mediated SNAP-25 phosphorylation.

Research Project

Project/Area Number 24240055
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionKitasato University

Principal Investigator

TAKAHASHI MASAMI  北里大学, 医学部, 名誉教授 (10318826)

Co-Investigator(Renkei-kenkyūsha) MIYAOKA Hitoshi  北里大学, 医学部, 教授 (40209862)
ITAKURA Makoto  北里大学, 医学部, 准教授 (30398581)
OKADA Daisuke  北里大学, 医学部, 講師 (10211806)
YAMAMORI Saori  北里大学, 医学部, 講師 (30464803)
AZUMA Sadahiro  北里大学, 医学部, 助教 (80348507)
KATAOKA Masakazu  信州大学, 工学部, 准教授 (90332676)
Research Collaborator WATANABE Shigeru  
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥39,260,000 (Direct Cost: ¥30,200,000、Indirect Cost: ¥9,060,000)
Fiscal Year 2014: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2013: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2012: ¥21,450,000 (Direct Cost: ¥16,500,000、Indirect Cost: ¥4,950,000)
Keywordsタンパク質リン酸化 / プロテインキナーゼC / SNAREタンパク質 / 開口放出 / てんかん / 不安用行動 / 脳波測定 / SNAP-25 / 遺伝子改変マウス / 不安様行動 / ピロカルピンモデル / BDNF / ノックインマウス / 行動異常 / 抗てんかん薬 / ドーパミン / ストレス
Outline of Final Research Achievements

Regulatory mechanisms and functional roles of SNAP-25 phosphorylation were studied using a knock-in mouse with a single amino acid substitution at a PKC-dependent phosphorylation site. We found that the dephosphorylation of SNAP-25 was mediated by PP2A through Ca2+-dependent and Ca2+-independent mechanisms, and SNAP-25 phosphorylation played a role in stress response of animals. The SNAP-25 mutant mouse exhibited several distinct phenotypes, including anxiety-like behavior and epileptogenesis. We found that anxiety-like behaviors appeared through several different mechanisms and dopamine D2 receptor was involved in some mechanisms. We conducted long-term continuous video electroencephalogram recordings of the mice and revealed the process of epileptogenesis and epileptic maturation in detail. We developed a unique drug administration system to free-moving mouse during continuous electroencephalogram recording, which would be useful for the discovery of new antiepileptic drugs.

Report

(4 results)
  • 2015 Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (21 results)

All 2016 2015 2014 2013 2012 Other

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 2 results,  Acknowledgement Compliant: 3 results) Presentation (9 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Dual mechanisms of rapid expression of anxiety-related behavior in pilocarpine-treated epileptic mice2016

    • Author(s)
      Otsuka S, Ohkido T, Itakura M, Watanabe S, Yamamori S, Iida Y, Saito M, Miyaoka H, Takahashi M
    • Journal Title

      Epilepsy Research

      Volume: 123 Pages: 55

    • DOI

      10.1016/j.eplepsyres.2016.04.007

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Epileptogenesis and epileptic maturation in phosphorylation site-specific SNAP-25 mutant mice2015

    • Author(s)
      Watanabe S, Yamamori S, Ohtsuka S, Saito M, Suzuki E, Kataoka M, Miyaoka H, Takahashi M
    • Journal Title

      Epilepsy Research

      Volume: 115 Pages: 30

    • DOI

      10.1016/j.eplepsyres.2015.05.004

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] BDNF pro-peptide actions facilitate hippocampal LTD and are altered by the common BDNF polymorphism Val66Met.2015

    • Author(s)
      Mizui T, Ishikawa Y, Kumanogoh H, Lume M, Matsumoto T, Hara T, Yamawaki S, Takahashi M, Shiosaka S, Itami C, Uegaki K, Saarma M, Kojima M.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 112 Issue: 23

    • DOI

      10.1073/pnas.1422336112

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Stress-induced phosphorylation of SNAP-25.2014

    • Author(s)
      Yamamori S, Sugaya D, Iida Y, Kokubo H, Itakura M, Suzuki E, Kataoka M, Miyaoka H, Takahashi M
    • Journal Title

      Neurosci Letter

      Volume: 561 Pages: 182-187

    • DOI

      10.1016/j.neulet.2013.12.044

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct association of the unique C-terminal tail of transmembrane AMPA receptor regulatory protein γ-8 with calcineurin.2014

    • Author(s)
      Itakura M, Watanabe I, Sugaya T, Takahashi M
    • Journal Title

      FEBS J

      Volume: 281 Issue: 5 Pages: 1366-1378

    • DOI

      10.1111/febs.12708

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tyrosine 402 Phosphorylation of Pyk2 Is Involved in Ionomycin-Induced Neurotransmitter Release.2014

    • Author(s)
      Zhang Z, Zhang Y, Mou M, Chu S, Chen X, He W, Guo X, Yuan Y, Takahashi M, Chen N
    • Journal Title

      PLoS ONE

      Volume: 9 Issue: 4 Pages: e94574-e94574

    • DOI

      10.1371/journal.pone.0094574

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protein phosphatase 2A dephosphorylates SNAP-25 through two distinct mechanisms in mouse brain synaptosomes.2013

    • Author(s)
      IIda Y
    • Journal Title

      Neurosci. Res.

      Volume: 75 Issue: 3 Pages: 184-189

    • DOI

      10.1016/j.neures.2013.01.002

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synaptosomal-associated protein 25 mutation induces immaturity of the dentate granule cells of adult mice.2013

    • Author(s)
      Ohira K, Kobayashi K, Toyama K, Nakamura HK, Shoji H, Takao K, Takeuchi R, Yamaguchi S, Kataoka M, Otsuka S, Takahashi M, Miyakawa T.
    • Journal Title

      Molecular Brain

      Volume: 6 Issue: 1 Pages: 12-12

    • DOI

      10.1186/1756-6606-6-12

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NMDA receptor-dependent recruitment of calnexin to the neuronal plasma membrane.2013

    • Author(s)
      Itakura M, Tsujimura J, Yamamori S, Ohkido T, Takahashi M
    • Journal Title

      Neurosci Lett

      Volume: 550 Pages: 173-178

    • DOI

      10.1016/j.neulet.2013.06.064

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Calmodulin-dependent regulation of neurotransmitter release differs in subsets of neuronal cells.2013

    • Author(s)
      Ando K, Kudo Y, Aoyagi K, Ishikawa R, Igarashi M, Takahashi M
    • Journal Title

      Brain Res

      Volume: 1535 Pages: 1-13

    • DOI

      10.1016/j.brainres.2013.08.018

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Accumulation of a-synuclein triggered by presynaptic dysfunction2012

    • Author(s)
      Nakata Y, Yasuda T, Fukaya M, Yamamori S, Itakura M, Nihira T, Hayakawa H, Kawanami A, Kataoka M, Nagai M, Sakagami H, Takahashi M, Mizuno Y, Mochizuki H
    • Journal Title

      J. Neurosci

      Volume: 32 Issue: 48 Pages: 17186-17196

    • DOI

      10.1523/jneurosci.2220-12.2012

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] ピロカルピンによって誘発されたてんかん重積後に、NMDA型受容体はサブユニット特異的に減少する2012

    • Author(s)
      板倉誠
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Annual Research Report
  • [Presentation] SNAP-25リン酸化部位変異マウスが示す異常行動の一部には、カテコールアミンが関与する2012

    • Author(s)
      飯田諭宜
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Annual Research Report
  • [Presentation] Calcium-binding protein calretinin is highly expressed in CA3 neurons of epileptized brain in pilocarpine model.2012

    • Author(s)
      大城戸太朗
    • Organizer
      The 11th Biennial Meeting of the Asian-Pacific Society for Neurochemistry/55th Annual Meeting of the Japanese Society for Neurochemistry
    • Place of Presentation
      神戸
    • Related Report
      2012 Annual Research Report
  • [Presentation] Stress induced phosphorylation of SNAP-252012

    • Author(s)
      山森早織
    • Organizer
      北米神経科学会大会
    • Place of Presentation
      ニューオリンズ(米国)
    • Related Report
      2012 Annual Research Report
  • [Presentation] げっ歯類BdnfアンチセンスRNAの機能解析

    • Author(s)
      熊ノ郷 晴子、水井 利幸、清末 和之、高橋 正身、小島 正己
    • Organizer
      Neuro 2013
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 海馬CA1領域でのシナプス前短期可塑性におけるSNAP-25のリン酸化の役割

    • Author(s)
      片山 憲和、山森 早織、深谷 昌弘、渡辺 雅彦、高橋 正身、真鍋 俊也
    • Organizer
      Neuro 2013
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 歯状回ニューロンの成熟異常を示すマウスの海馬におけるBDNF-MAPK シグナル経路の調節異常

    • Author(s)
      小清水 久嗣、大平 耕司、萩原 英雄、高雄 啓三、高木 豪、片岡 正和、石井 俊輔、高橋 正身、宮川 剛
    • Organizer
      Neuro 2013
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] てんかんを自然発症するモデルマウスの脳波の長期間解析

    • Author(s)
      高橋正身、渡辺滋、斎藤正範、山森早織、飯田諭宜、宮岡等
    • Organizer
      第47回日本てんかん学会学術集会
    • Place of Presentation
      北九州
    • Related Report
      2013 Annual Research Report
  • [Presentation] PKC-dependent phosphorylation of SNAP-25 is essential for the positive regulation of dopamine release in mouse brain。

    • Author(s)
      Saori Yamamori, Suguru Kanno and Masami Takahashi
    • Organizer
      北米神経科学会大会
    • Place of Presentation
      サンディエゴ(米国)
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] 小動物収容装置、小動物実験システム及び小動物実験方法2014

    • Inventor(s)
      渡辺 滋
    • Industrial Property Rights Holder
      渡辺 滋
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-197454
    • Filing Date
      2014-09-26
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-15   Modified: 2019-07-29  

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