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Mechanisms of memory impairment caused by the increase in phosphorylated tau

Research Project

Project/Area Number 16K21328
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Nerve anatomy/Neuropathology
Environmental physiology(including physical medicine and nutritional physiology)
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

Yagishita Sosuke  国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第五部, 室長 (30585592)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsタウ / アルツハイマー病 / 神経活動 / 睡眠時無呼吸症候群 / 間欠的低酸素負荷 / タウオパチー / 間欠的低酸素 / PICK1
Outline of Final Research Achievements

Neurofibrillary tangles are composed of abnormally phosphorylated tau, a microtubule-associated protein. Neurofibrillary tangles are present in entorhinal cortex or hippocampus in normal aging brains, and are present in cerebral cortex in Alzheimer disease brains. However, the mechanism of neurofibrillary tangle formation is still unknown. In this study, I investigated how the level of phosphorylated tau alter in physiological condition. I found that the level of phosphorylated tau alter according to neural activity, and the extent of neural activity-dependent new gene expressions. This result made me to generate a condition in which the level of phosphorylated tau increased. I found that consecutive increase in phosphorylated tau led to increase in detergent-insoluble tau, which is thought to be the pre-accumulated form.

Academic Significance and Societal Importance of the Research Achievements

リン酸化タウの蓄積は正常な加齢でも見られ,神経細胞を長年使った結果と捉えることもできる。本研究では,リン酸化タウが増減する仕組みを理解し,神経細胞に生来備わった性質の解明を目指したものである。これは脳の加齢の実態を知り,認知症との境界を理解することである。その結果,従来の定説とは異なり,リン酸化タウは神経活動に伴って普段から増減し,神経活動量が変わることでリン酸化タウが増加した状態が持続することが分かった。そしてその状態が持続すると,蓄積の前段階と考えられるタウが増加する可能性を見出した。このような状態が特定の範囲を超えて広範囲で起きているのが認知症という新たな捉え方を提案するものである。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (12 results)

All 2019 2017 2016

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (6 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Intermittent hypoxia produces Alzheimer disease?2017

    • Author(s)
      Yagishita S, Hirasawa A
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 26 Pages: 41786-41787

    • DOI

      10.18632/oncotarget.18214

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease2017

    • Author(s)
      Yamamoto S, Yamashina K, Ishikawa M, Gotoh M, Iwasa K, Yagishita S, Maruyama K, Murakami-Murofushi K, Yoshikawa K
    • Journal Title

      Journal of Neuroinflammation

      Volume: 14 Issue: 1 Pages: 142-142

    • DOI

      10.1186/s12974-017-0923-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treatment of intermittent hypoxia increases phosphorylated tau in the hippocampus via biological processes common to aging.2017

    • Author(s)
      Yagishita S, Suzuki S, Yoshikawa K, Iida K, Hirata A, Suzuki M, Takashima A, Maruyama K, Hirasawa A, Awaji T.
    • Journal Title

      Mol Brain

      Volume: 10 Issue: 1 Pages: 2-2

    • DOI

      10.1186/s13041-016-0282-7

    • NAID

      120005971848

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Excitotoxicity-induced prostaglandin D2 production induces sustained microglial activation and delayed neuronal death.2017

    • Author(s)
      Iwasa K, Yamamoto S, Yagishita S, Maruyama K, Yoshikawa K.
    • Journal Title

      J Lipid Res.

      Volume: 58 Issue: 4 Pages: 649-655

    • DOI

      10.1194/jlr.m070532

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Specific combinations of presenilins and Aph1s affect the substrate specificity and activity of γ-secretase.2016

    • Author(s)
      YOnemura, Y., Futai, E., Yagishita, S., Aether, C., and Ishiura, S.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 478 Issue: 4 Pages: 1751-1757

    • DOI

      10.1016/j.bbrc.2016.09.018

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Perturbed Calcineurin-NFAT Signaling Is Associated with the Development of Alzheimer's Disease.2016

    • Author(s)
      Asai M, Kinjo A, Kimura S, Mori R, Kawakubo T, Shirotani K, Yagishita S, Maruyama K, Iwata N.
    • Journal Title

      Biol Pharm Bull.

      Volume: 39 Pages: 1646-1652

    • NAID

      130005598494

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 社会性に関わるシナプス接着分子に対する性ホルモンの影響2019

    • Author(s)
      柳下-姜 楠、原田 美海、上北 朋子、丸山 敬、伊海 結貴、越本 知大、柳下 聡介
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] INTERMITTENT HYPOXIA INCREASES TAU PHOSPHORYLATION VIA BIOLOGICAL PROCESSES COMMON TO AGING: POTENTIAL LINK BETWEEN SLEEP-DISORDERED BREATHING AND ALZHEIMER DISEASE,2017

    • Author(s)
      Sosuke Yagishita
    • Organizer
      6th Mediterranean Neuroscience Society Conference
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 間欠的低酸素負荷は,加齢とアルツハイマー病との関連を研究するための新たなモデルである2017

    • Author(s)
      栁下聡介,鈴木星也,淡路健雄,平澤明,丸山敬
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Presentation] GSK-3βが関与するPICK1のリン酸化は,GluA2との結合を制御する2016

    • Author(s)
      柳下聡介,村山美由紀,海老原朋江,丸山敬,高島明彦
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      横浜
    • Related Report
      2016 Research-status Report
  • [Presentation] 内在性リン酸化タウ増加モデルのマイクロアレイ解析2016

    • Author(s)
      栁下聡介,鈴木星也,吉川圭介,飯田桂子,平田理子,鈴木正彦,高島明彦,丸山敬,平澤明,淡路健雄
    • Organizer
      第35回日本認知症学会
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
  • [Presentation] GSK-3β-mediated phosphorylation of PICK1 regulates the GluA2-PICK1 interaction2016

    • Author(s)
      Sosuke Yagishita, Miyuki Murayama, Tomoe Ebihara, Kei Maruyama, Akihiko Takashima
    • Organizer
      Society for Neuroscience
    • Place of Presentation
      San Diego
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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