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Biological crosstalk of between mastication and brain function

Research Project

Project/Area Number 16H05506
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Nakashima Tomoki  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (00346959)

Research Collaborator Ono Takehito  
Hayashi Mikihito  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Keywords咀嚼・運動機能 / 高次脳機能 / 記憶・学習 / 遺伝子改変マウス
Outline of Final Research Achievements

Cognitive dysfunction is a public health issue, which is one of the main contributing factors for need-of-care, afflicting patients and their caretakers. It is well accepted that physical activity is in close relationship with brain function. Accumulating data has indicated that exercise training, crosstalk the muscle and skeletal system, can improve brain functions both directly and indirectly via the alleviation of the diseases underlying. Recently, mechanisms bridging brain functions and physical exercises have been clarified. We have investigate the biological crosstalk the muscle and skeletal system through approach combined with comprehensive analysis and sophisticated genetically modified mouse system. This project will not only enable a better understanding of the regulatory system of higher biological functions of neuropsychiatric diseases, but also provide a molecular basis for developing new therapeutic strategies and effective exercise therapy for these diseases.

Academic Significance and Societal Importance of the Research Achievements

咀嚼・運動機能と学習・記憶形成など高次機能の連関クロストークの実態に迫り、その制御機構を理解するためには、これまでにない新規モデル動物の開発と制御分子の網羅的解析が、ブレイクスルーポイントになった。本研究では、咀嚼機能の破綻や寝たきり状態を生体レベルで再現するためモデルマウスを構築・解析することで、咀嚼・運動機能の変動と高次機能の連関を司る遺伝子の基盤情報を得た。本研究から導かれる成果は、認知症や記憶障害をはじめ、統合失調症やうつ病など様々な高次機能疾患の発症機構の解明と革新的な治療戦略の提示、早期診断マーカーへの応用など、医療現場に直結する基盤技術の確立に貢献することが期待される。

Report

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

    (30 results)

All 2019 2018 2017 2016

All Journal Article (17 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 13 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) (of which Int'l Joint Research: 1 results,  Invited: 13 results)

  • [Journal Article] Forceful mastication activates osteocytes and builds a stout jawbone2019

    • Author(s)
      Masamu Inoue、Takehito Ono、Yoshitaka Kameo、Fumiyuki Sasaki、Takashi Ono、Taiji Adachi、Tomoki Nakashima
    • Journal Title

      Scientific Reports

      Volume: 9(1) Issue: 1 Pages: 1-12

    • DOI

      10.1038/s41598-019-40463-3

    • NAID

      120006773166

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autoregulation of Osteocyte Sema3A Orchestrates Estrogen Action and Counteracts Bone Aging2019

    • Author(s)
      Hayashi Mikihito、Nakashima Tomoki、Yoshimura Noriko、Okamoto Kazuo、Tanaka Sakae、Takayanagi Hiroshi
    • Journal Title

      Cell Metabolism

      Volume: 29 Issue: 3 Pages: 627-637

    • DOI

      10.1016/j.cmet.2018.12.021

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Arginine methylation controls the strength of γc-family cytokine signaling in T cell maintenance2018

    • Author(s)
      Inoue Maia、Okamoto Kazuo、Terashima Asuka、Nitta Takeshi、Muro Ryunosuke、Negishi-Koga Takako、Kitamura Toshio、Nakashima Tomoki、Takayanagi Hiroshi
    • Journal Title

      Nature Immunology

      Volume: 19 Issue: 11 Pages: 1265-1276

    • DOI

      10.1038/s41590-018-0222-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of hematopoietic cell kinase ameliorates the bone destruction associated with inflammation2018

    • Author(s)
      Kim Yusoon、Hayashi Mikihito、Ono Takehito、Yoda Tetsuya、Takayanagi Hiroshi、Nakashima Tomoki
    • Journal Title

      Modern Rheumatology

      Volume: - Issue: 1 Pages: 1-8

    • DOI

      10.1080/14397595.2018.1553266

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Host defense against oral microbiota by bone-damaging T cells2018

    • Author(s)
      Tsukasaki Masayuki、Komatsu Noriko、Nagashima Kazuki、Nitta Takeshi、Pluemsakunthai Warunee、Shukunami Chisa、Iwakura Yoichiro、Nakashima Tomoki、Okamoto Kazuo、Takayanagi Hiroshi
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 701-701

    • DOI

      10.1038/s41467-018-03147-6

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reduced Mastication Impairs Memory Function2017

    • Author(s)
      Fukushima-Nakayama Y.、Ono Takehito、Hayashi M.、Inoue M.、Wake H.、Ono Takashi、Nakashima T.
    • Journal Title

      Journal of Dental Research

      Volume: 96 Issue: 9 Pages: 1058-1066

    • DOI

      10.1177/0022034517708771

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Osteocyte regulation of orthodontic force-mediated tooth movement via RANKL expression2017

    • Author(s)
      Shoji-Matsunaga Ayumi、Ono Takehito、Hayashi Mikihito、Takayanagi Hiroshi、Moriyama Keiji、Nakashima Tomoki
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 8753-8753

    • DOI

      10.1038/s41598-017-09326-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exercise and brain function2017

    • Author(s)
      Ono T, Nakashima T
    • Journal Title

      Clin Calcium

      Volume: 28 Pages: 57-57

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Targeted deletion of RANKL in M cell inducer cells by the Col6a1-Cre driver.2017

    • Author(s)
      Nagashima K, Sawa S, Nitta T, Prados A, Koliaraki V, Kollias G, Nakashima T, Takayanagi H.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 493 Issue: 1 Pages: 437-443

    • DOI

      10.1016/j.bbrc.2017.09.004

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota.2017

    • Author(s)
      Nagashima K, Sawa S, Nitta T, Tsutsumi M, Okamura T, Penninger JM, Nakashima T, Takayanagi H
    • Journal Title

      Nature Immunology

      Volume: 印刷中 Issue: 6 Pages: 675-682

    • DOI

      10.1038/ni.3732

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Osteoimmunology: The Conceptual Framework Unifying the Immune and Skeletal Systems2017

    • Author(s)
      Okamoto Kazuo、Nakashima Tomoki、Shinohara Masahiro、Negishi-Koga Takako、Komatsu Noriko、Terashima Asuka、Sawa Shinichiro、Nitta Takeshi、Takayanagi Hiroshi
    • Journal Title

      Physiological Reviews

      Volume: 97 Issue: 4 Pages: 1295-1349

    • DOI

      10.1152/physrev.00036.2016

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sepsis-induced osteoblast ablation causes immunodeficiency2016

    • Author(s)
      Terashima, A., Okamoto, K., Nakashima, T., Akira, S., Ikuta, K. and Takayanagi, H.
    • Journal Title

      Immunity

      Volume: 44 Issue: 6 Pages: 1434-1443

    • DOI

      10.1016/j.immuni.2016.05.012

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of biallelic LRRK1 mutations in osteosclerotic metaphyseal dysplasia and evidence for locus heterogeneity2016

    • Author(s)
      Iida A, Xing W, Docx MK, Nakashima T, Wang Z, Kimizuka M, Van Hul W, Rating D, Spranger J, Ohashi H, Miyake N, Matsumoto N, Mohan S, Nishimura G, Mortier G, Ikegawa S
    • Journal Title

      J Med Genet

      Volume: 53 Issue: 8 Pages: 568-574

    • DOI

      10.1136/jmedgenet-2016-103756

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] IL-17-producing γδ T cells enhance bone regeneration2016

    • Author(s)
      Ono T, et al.
    • Journal Title

      Nat Commun

      Volume: 7 Issue: 1 Pages: 10928-10928

    • DOI

      10.1038/ncomms10928

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 骨代謝とメカノバイオロジー2016

    • Author(s)
      中島友紀
    • Journal Title

      CLINICAL CALCIUM

      Volume: 26 Pages: 35-45

    • Related Report
      2016 Annual Research Report
  • [Journal Article] RANKLとオステオネッワーク2016

    • Author(s)
      中島友紀
    • Journal Title

      CLINICAL CALCIUM

      Volume: 26 Pages: 1135-1142

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 骨粗鬆症~骨の恒常性と破綻~2016

    • Author(s)
      中島友紀
    • Journal Title

      医学のあゆみ

      Volume: 257 Pages: 985-991

    • Related Report
      2016 Annual Research Report
  • [Presentation] ステロイド性骨粗鬆症の発症メカニズム2018

    • Author(s)
      中島友紀
    • Organizer
      第20回日本骨粗鬆症学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 骨細胞による骨リモデリングの制御2018

    • Author(s)
      中島友紀
    • Organizer
      第60回歯科基礎医学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] RANKL Biology -骨代謝研究を越えて-2018

    • Author(s)
      中島友紀
    • Organizer
      第39回 日本炎症・再生医学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 骨恒常性の制御機構2018

    • Author(s)
      中島友紀
    • Organizer
      第16回 ナノ学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Bone homeostasis and mechanomedicine2017

    • Author(s)
      中島友紀
    • Organizer
      第95回 日本生理学会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 骨細胞による骨リモデリングの制御機構2017

    • Author(s)
      中島友紀
    • Organizer
      第59回歯科基礎医学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 骨恒常性のバイオロジー2017

    • Author(s)
      中島友紀
    • Organizer
      第3回日本筋学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 骨恒常性とメカノバイオロジー2017

    • Author(s)
      中島友紀
    • Organizer
      56回 日本生体医工学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] RANKL Biology -骨破壊から新たな制御システムまで-2016

    • Author(s)
      中島友紀
    • Organizer
      日本リウマチ学会全国中央教育研修会大阪大会
    • Place of Presentation
      大阪
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 骨細胞による骨リモデリングの制御2016

    • Author(s)
      中島友紀
    • Organizer
      第43回日本臨床バイオメカニクス学会
    • Place of Presentation
      札幌
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] RANKLを標的とした治療戦略2016

    • Author(s)
      中島友紀
    • Organizer
      第34回日本骨代謝学会
    • Place of Presentation
      大阪
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 骨リモデリングの制御機構2016

    • Author(s)
      中島友紀
    • Organizer
      第2回日本骨免疫学会
    • Place of Presentation
      沖縄
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] RANKL Biology2016

    • Author(s)
      中島友紀
    • Organizer
      日本リウマチ学会総会 アニュアルコースレクチャー
    • Place of Presentation
      横浜
    • Related Report
      2016 Annual Research Report
    • Invited

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

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