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Elucidation of sleep bruxism mechanism using chemogenetic analysis of neural circuit assembly

Research Project

Project/Area Number 18K09527
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57010:Oral biological science-related
Research InstitutionShowa University

Principal Investigator

Mochizuki Ayako  昭和大学, 歯学部, 講師 (10453648)

Co-Investigator(Kenkyū-buntansha) 井上 富雄  昭和大学, 歯学部, 教授 (70184760)
船戸 弘正  筑波大学, 国際統合睡眠医科学研究機構, 客員教授 (90363118)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords睡眠時ブラキシズム / セロトニン / SSRI / うつ病 / 光遺伝学 / 薬理遺伝学 / ブラキシズム / Disc1
Outline of Final Research Achievements

Bruxism is a multifactorial disease caused by involuntary masticatory muscle activities such as clenching and clenching, in which various factors such as stress and drug administration are involved in a complex manner. However, details regarding the related mechanism(s) remain largely unknown. We found that administration of a serotonin reuptake inhibitor (SSRI), a type of antidepressant known to induce bruxism, increased masseter muscle activity during non-REM sleep. Using that phenomenon as an index, the activity of GABA neurons present in ventrolateral periaqueductal gray matter (vlPAG) was altered by employing a DREADD system, though there was nearly no subsequent alteration in masseter muscle activity. These results suggest that vlPAG GABA neurons may not be involved in SSRI-induced masseter muscle activity.

Academic Significance and Societal Importance of the Research Achievements

多くの国民が悩んでいる歯ぎしりや食いしばり(総称してブラキシズムと言う)の治療法を開発するために、ブラキシズムがどのようにして起こるのかメカニズムを探索している。私たちは、ブラキシズムの誘発因子の1つである抗うつ薬、セロトニン再取り込み阻害薬(SSRI)をマウスに投与し、ノンレム睡眠中の顎を動かす筋肉の活動性が上昇することを発見した。この現象は、中脳水道周囲灰白質腹外側部という脳の一部分に存在するGABAニューロンの活動状態を人為的に変化させても、ほとんど変化がなかった。このように、顎を動かす筋肉に脳のどの部分が影響しているのかを調べ、ブラキシズムの治療法の開発に役立てようと考えている。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (40 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 3 results) Presentation (28 results) (of which Int'l Joint Research: 8 results) Remarks (2 results)

  • [Journal Article] Developmental changes in GABAergic and glycinergic synaptic transmission to rat motoneurons innervating jaw-closing and jaw-opening muscles2022

    • Author(s)
      Noguchi Tsuyoshi、Nakamura Shiro、Nakayama Kiyomi、Mochizuki Ayako、Dantsuji Masanori、Ihara Yoshiaki、Takahashi Koji、Inoue Tomio
    • Journal Title

      Brain Research

      Volume: 1777 Pages: 147753-147753

    • DOI

      10.1016/j.brainres.2021.147753

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Postnatal Maturation of Glutamatergic Inputs onto Rat Jaw-closing and Jaw-opening Motoneurons2022

    • Author(s)
      Nakamura Shiro、Kajiwara Risa、Noguchi Tsuyoshi、Nakayama Kiyomi、Mochizuki Ayako、Dantsuji Masanori、Sarkar Avijite Kumer、Inoue Tomio
    • Journal Title

      Neuroscience

      Volume: 480 Pages: 42-55

    • DOI

      10.1016/j.neuroscience.2021.11.016

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intrinsic properties and synaptic connectivity of Phox2b-expressing neurons in rat rostral parvocellular reticular formation2021

    • Author(s)
      Kajiwara Risa、Nakamura Shiro、Ikeda Keiko、Onimaru Hiroshi、Yoshida Atsushi、Tsutsumi Yumi、Nakayama Kiyomi、Mochizuki Ayako、Dantsuji Masanori、Nishimura Akiko、Tachikawa Satoshi、Iijima Takehiko、Inoue Tomio
    • Journal Title

      Neuroscience Research

      Volume: - Pages: 41-51

    • DOI

      10.1016/j.neures.2021.12.009

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Responses evoked by electrical stimulation of the brainstem reticular formation in the jaw-opening and hypoglossal motor nerves of an arterially perfused rat preparation2020

    • Author(s)
      Ofuji Takuo、Nakayama Kiyomi、Nakamura Shiro、Mochizuki Ayako、Dantsuji Masanori、Ishiguro Mitsunori、Yamamoto Matsuo、Inoue Tomio
    • Journal Title

      Neuroscience Letters

      Volume: 738 Pages: 135400-135400

    • DOI

      10.1016/j.neulet.2020.135400

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] 5-HT2A receptor activation enhances NMDA receptor-mediated glutamate responses therough Src kinase in the dendrites of rat jaw-closing motoneurons.2019

    • Author(s)
      Dantsuji M, Nakamura S, Nakayam, K, Mochizuki A, Park SK, Bae YC, Ozeki M, Inoue T.
    • Journal Title

      J. Physiol.

      Volume: 印刷中 Issue: 9 Pages: 2565-2589

    • DOI

      10.1113/jp275440

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Serotonin1B receptor-mediated presynaptic inhibition of proprioceptive sensory inputs to jaw-closing motoneurons.2019

    • Author(s)
      Nagata A, Nakayama K, Nakamura S, Mochizuki A, Gemba C, Aoki R, Dantsuji M, Maki K, Inoue T.
    • Journal Title

      Brain Res Bull.

      Volume: 149 Pages: 260-267

    • DOI

      10.1016/j.brainresbull.2019.05.001

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Enhancement of swallowing motor activity by the ACE inhibitor imidapril in an arterially perfused rat preparation.2019

    • Author(s)
      Moriya T, Nakayama K, Nakamura S, Mochizuki A, Ofuji T, Shirota T, Inoue T.
    • Journal Title

      Eur J Pharmacol.

      Volume: 861 Pages: 172601-172601

    • DOI

      10.1016/j.ejphar.2019.172601

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Nanomechanical characterization of time-dependent deformation/recovery on human dentin caused by radiation-induced glycation2019

    • Author(s)
      Tobe Takuma、Shibata Yo、Mochizuki Ayako、Shimomura Naofumi、Zhou Jun、Wurihan、Tanaka Reina、Ikeda Sachiko、Zhang Zhongpu、Li Qing、Inoue Tomio、Miyazaki Takashi
    • Journal Title

      Journal of the Mechanical Behavior of Biomedical Materials

      Volume: 90 Pages: 248-255

    • DOI

      10.1016/j.jmbbm.2018.10.015

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The inhibition of malignant melanoma cell invasion of bone by the TLR7 agonist R848 is dependent upon pro-inflammatory cytokines produced by bone marrow macrophages2018

    • Author(s)
      Manome Yoko、Suzuki Dai、Mochizuki Ayako、Saito Emi、Sasa Kiyohito、Yoshimura Kentaro、Inoue Tomio、Takami Masamichi、Inagaki Katsunori、Funatsu Takahiro、Kamijo Ryutaro
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 52 Pages: 29934-29943

    • DOI

      10.18632/oncotarget.25711

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of orexin in lipid accumulation in the liver2018

    • Author(s)
      Mochizuki Ayako, Nakayama Kiyomi, Nakamura Shiro, Dantsuji Masanori, Kamijo Ryutaro, Shioda Seiji, Sakurai Takeshi, Ozeki Masahiko, Inoue Tomio.
    • Journal Title

      Journal of Oral Biosciences

      Volume: 印刷中

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] ラット小細胞性網様体に存在するPhox2b発現細胞の生理学的・形態学的特性解析2022

    • Author(s)
      梶原里紗,中村史朗,池田啓子,鬼丸洋,吉田篤,堤友美,中山希世美,望月文子,壇辻昌典,飯島毅彦,井上富雄
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Optogenetic activation of serotonergic neurons in the dorsal raphe nucleus changes masticatory movements in mice2021

    • Author(s)
      Dantsuji M, Mochizuki A, Nakayama K, Nakamura S, Kanamaru M, Izumizaki M, Tanaka KF, Inoue T
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 小細胞性網様体吻側領域に存在するPhox2b陽性ニューロンの電気生理学的・形態学的解析2021

    • Author(s)
      梶原里紗,中村史朗,池田啓子,鬼丸洋,中山希世美,望月文子,壇辻昌典,西村晶子,立川哲史,飯島毅彦,井上富雄
    • Organizer
      第68回昭和大学学士会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 閉口筋および開口筋運動ニューロンにおける抑制性シナプス伝達様式の生後変化2021

    • Author(s)
      野口 毅,中村 史朗,中山 希世美,望月 文子,壇辻 昌典,伊原 良明,髙橋 浩二,井上 富雄
    • Organizer
      第98回日本生理学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 咬筋運動ニューロン樹状突起における5-HT2A受容体の活性化はSrcを介してGluN2Aを含むNMDA受容体の機能を亢進する2020

    • Author(s)
      壇辻昌典,中村史朗,中山希世美,望月文子,井上富雄
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 小細胞性網様体に存在するPhox2陽性ニューロンの電気生理学的・形態学的解析2020

    • Author(s)
      梶原里紗,中村史朗,中山希世美,望月文子,壇辻昌典,立川哲史,飯島毅彦,井上富雄
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 閉口筋運動ニューロンにおける抑制性シナプス伝達の生後変化2020

    • Author(s)
      野口毅,中村史朗,中山希世美,望月文子,壇辻昌典,井上富雄
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Responses evoked by electrical stimulation of the brainstem reticular formation in the mylohyoid and hypoglossal motor nerves of an arterially perfused rat preparation.2020

    • Author(s)
      Ofuji T, Nakayama K, Nakamura S, Mochizuki A, Dantsuji M, Ishiguro M, Yamamoto M, Inoue T
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 除脳動脈ラット標本を用いた嚥下改善薬の効果の検討2020

    • Author(s)
      守谷崇,中山希世美,中村史朗,望月文子,壇辻昌典,井上富雄
    • Organizer
      第43回日本嚥下医学会学術講演会
    • Related Report
      2020 Research-status Report
  • [Presentation] 除脳ラット動脈灌流標本を用いた咀嚼様リズム神経活動の誘発.2019

    • Author(s)
      大藤拓生, 中山希世美, 中村史朗, 望月文子, 壇辻昌典, 井上富雄.
    • Organizer
      日本顎口腔機能学会第63回学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Serotonin1b receptor mediated presynaptic inhibition of jaw closing motoneurons.2019

    • Author(s)
      Nakayama K, Nagata A, Nakamura S, Mochizuki A, Dantsuji M, Maki K, Inoue T.
    • Organizer
      Society for Neuroscience 49th annual meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] マウス咬筋の筋活動に対するSSRIの影響.2019

    • Author(s)
      望月文子,池田美菜子,中村史朗,中山希世美,壇辻昌典,加藤隆史,馬場一美,井上富雄.
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 嚥下関連筋支配神経の活動に対するイミダプリルの効果.2019

    • Author(s)
      守谷崇, 中山希世美, 中村史朗, 望月文子, 壇辻昌典, 井上富雄.
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Serotonin1B receptors are involved in presynaptic inhibition of proprioceptive afferent transmission to jaw-closing motoneurons.2019

    • Author(s)
      Inoue T, Nagata A, Nakayama K, Dantsuji M, Nakamura S, Mochizuki A, Maki K.
    • Organizer
      IBRO2019 (The 10th IBRO World Congress of Neuroscience)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Presynaptic Activation of 5-HT1B Receptors Inhibits Proprioceptive Sensory Inputs to Jaw-Closing Motoneurons.2019

    • Author(s)
      Inoue T, Nagata A, Nakayama K, Dantsuji M, Nakamura S, Mochizuki A, Maki K.
    • Organizer
      FENS Regional Meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 嚥下関連筋支配神経への嚥下改善薬の効果.2019

    • Author(s)
      守谷崇, 中山希世美, 中村史朗, 望月文子, 壇辻昌典, 代田達夫, 井上 富雄.
    • Organizer
      日本顎口腔機能学会第62回学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Effects of optogenetic inhibition of 5-HT neurons in the dorsal raphe nucleus on respiratory control2019

    • Author(s)
      Kanamaru M, Tsukada M, Yoshikawa A, Onimaru H, Mochizuki A,Sunagawa M, Inoue T, Izumizaki M
    • Organizer
      The 9th Federation of the Asian and Oceanian Physiological Societies Congress in conjunction with the 96th Annual Meeting of the Physiological Society of Japan, Kobe.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Phox2b-expressing neurons in the rat reticular formation dorsal to the trigeminal motor nucleus2019

    • Author(s)
      Nakamura S, Nagoya K, Ikeda K, Onimaru H, Kawakami K, Nakayama K, Mochizuki A, Dantsuji M, Inoue T
    • Organizer
      The 9th Federation of the Asian and Oceanian Physiological Societies Congress in conjunction with the 96th Annual Meeting of the Physiological Society of Japan, Kobe.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 嚥下改善薬の投与による嚥下への影響2018

    • Author(s)
      守谷崇,中山希世美,望月文子,中村史朗,代田達夫, 井上富雄
    • Organizer
      第65回昭和大学学士会総会,東京
    • Related Report
      2018 Research-status Report
  • [Presentation] Effects of pharmacological agents administered for swallowing disorders on swallowing motor activity in nerves innervating infrahyoid and laryngeal muscles.2018

    • Author(s)
      Moriya T, Nakayama K, Nakamura S, Mochizuki A, Shirota T, Inoue T
    • Organizer
      Society for Neuroscience 48th annual meeting, San Diego, U.S.A.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Activation of 5-HT2A receptor enhances function of GluN2A-containing NMDA receptor via Src kinase in dendrites of rat jaw-closing motoneurons2018

    • Author(s)
      Dantsuji M, Nakamura S, Mochizuki A, Nakayama K, Kiyomoto M, S. K. Park, Y. J. Bae, Ozeki M, Inoue T.
    • Organizer
      Society for Neuroscience 48th annual meeting, San Diego, U.S.A.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 閉口筋および開口筋運動ニューロンへの興奮性シナプス伝達の生後発達様式の比較2018

    • Author(s)
      中村史朗,中山希世美,望月文子,壇辻昌典,井上富雄
    • Organizer
      日本顎口腔機能学会第 61 回学術大会,東京
    • Related Report
      2018 Research-status Report
  • [Presentation] マウスの脂質代謝におけるオレキシンの影響2018

    • Author(s)
      望月文子,中村史朗,中山希世美,壇辻昌典,井上富雄
    • Organizer
      第60回歯科基礎医学会学術大会,福岡
    • Related Report
      2018 Research-status Report
  • [Presentation] 発達期における閉口筋および開口筋運動ニューロンのグルタミン酸入力比較2018

    • Author(s)
      中村史朗,中山希世美,望月文子,壇辻昌典,井上富雄
    • Organizer
      第60回歯科基礎医学会学術大会,福岡
    • Related Report
      2018 Research-status Report
  • [Presentation] マウスの睡眠覚醒ステージにおける咬筋活動に対するSSRIの影響2018

    • Author(s)
      池田美菜子,望月文子,中村史朗,中山希世美,馬場一美,井上富雄
    • Organizer
      第60回歯科基礎医学会学術大会,福岡
    • Related Report
      2018 Research-status Report
  • [Presentation] 咬筋運動ニューロン樹状突起のグルタミン酸応答に対するセロトニンの効果2018

    • Author(s)
      壇辻昌典,中村史朗,望月文子,中山希世美,尾関雅彦,井上富雄
    • Organizer
      第60回歯科基礎医学会学術大会,福岡
    • Related Report
      2018 Research-status Report
  • [Presentation] 5-HT2A receptor mediates enhancement of NMDA receptor function via Src pathway in dendrites of jaw-closing motoneurons in rats2018

    • Author(s)
      Dantsuji M, Nakamura S, Mochizuki A, Nakayama K, Kiyomoto M, S. K. Park, Y. J. Bae, Ozeki M, Inoue T.
    • Organizer
      11th Forum of Neuroscience, Berlin, Germany.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] マウスの睡眠覚醒ステージにおける咬筋活動に対するSSRIの影響2018

    • Author(s)
      池田美菜子,望月文子,中村史朗,中山希世美,馬場一美,井上富雄
    • Organizer
      日本顎口腔機能学会第60回学術大会,神奈川
    • Related Report
      2018 Research-status Report
  • [Remarks] 昭和大学歯学部口腔生理学講座

    • URL

      http://www10.showa-u.ac.jp/~oralphys/index.html

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
  • [Remarks] http://www10.showa-u.ac.jp/~oralphys/

    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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