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Development of an anorexia animal model using an arterially perfused decorticated mouse preparation

Research Project

Project/Area Number 19K22726
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 57:Oral science and related fields
Research InstitutionShowa University

Principal Investigator

Inoue Tomio  昭和大学, 歯学部, 教授 (70184760)

Co-Investigator(Kenkyū-buntansha) 中村 史朗  昭和大学, 歯学部, 准教授 (60384187)
中山 希世美  昭和大学, 歯学部, 講師 (00433798)
望月 文子  昭和大学, 歯学部, 講師 (10453648)
壇辻 昌典  昭和大学, 歯学部, 助教 (60826634)
Project Period (FY) 2019-06-28 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywords食欲 / 動脈灌流標本 / 嚥下 / 食欲不振 / 大脳除去ラット動脈灌流標本 / グレリン / 咀嚼 / 腕傍核
Outline of Research at the Start

高齢者の食欲不振は、要介護状態にいたる重大なリスク要因となる。食欲不振の真の原因の解明は、動物の摂食量の減少を指標にする従来の研究手法では難しかった。最近私たちは、標本の全身状態に関係なく中枢神経系や頭部組織の活性を保つことができる大脳除去動物の動脈灌流標本を開発した。そこで本研究は、摂食行動を制御する基本的な神経回路が存在するとされる視床下部から脳幹に着目し、視床下部や脳幹が“食欲不振の状態”になると動脈灌流標本の咀嚼様運動や嚥下様運動が起こりにくくなると仮定し、これらの運動の誘発を指標に食欲不振を起こす条件とその背景にある神経メカニズムを探り、新規の食欲不振動物実験モデルの確立を目指す。

Outline of Final Research Achievements

Anorexia is caused by physical and emotional diseases, as well as aging. It is not clear that neural mechanisms underlying appetite control because the amount of food intake which is used for the the analysis in conventional animal models, is often affected by health condition of the subjects. In this study, we analyzed the effects of several physiologically active substances that have been ascribed to affect the amount of food intake on swallowing-like movement induced in an arterially perfused decerebrated rat preparation to establish a new experimental model to analyze neural mechanisms underlying appetite control. Application of ghrelin increased swallowing-like movement by 31%. Thus, it is possible that the arterially perfused decerebrated rat preparation may be used for analyze neural mechanisms underlying appetite control.

Academic Significance and Societal Importance of the Research Achievements

摂食行動を司る神経機構を解明するために、従来の動物の摂食量を指標にした解析方法では、覚醒レベルや体調などの変動要因が数多く存在する。本研究は、除脳によって精神的、心理的な食欲不振の要因を取り除き、口腔内への蒸留水注入によって誘発された嚥下様運動を指標とすることで、変動要因を極力減らし、食欲不振に関わるニューロン機構を解析できる。さらに、食欲不振と摂食行動の実行システム(嚥下)との関連も解析できる。本実験によって食欲不振だけでなく過食の神経メカニズムについても新たな発想の画期的な研究手法の開発につながる可能性があり、がん患者や高齢者の食欲不振の治療法の開発につながる可能性がある。

Report

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

    (46 results)

All 2022 2021 2020 2019 Other

All Journal Article (10 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 10 results,  Open Access: 4 results) Presentation (32 results) (of which Int'l Joint Research: 11 results,  Invited: 1 results) Book (3 results) Remarks (1 results)

  • [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] 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] Increased excitability of human iPSC-derived neurons in HTR2A variant-related sleep bruxism2022

    • Author(s)
      Sarkar Avijite Kumer、Nakamura Shiro、Nakai Kento、Sato Taro、Shiga Takahiro、Abe Yuka、Hoashi Yurie、Inoue Tomio、Akamatsu Wado、Baba Kazuyoshi
    • Journal Title

      Stem Cell Research

      Volume: 59 Pages: 102658-102658

    • DOI

      10.1016/j.scr.2022.102658

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells2021

    • Author(s)
      Nakai Kento、Shiga Takahiro、Yasuhara Rika、Sarkar Avijite Kumer、Abe Yuka、Nakamura Shiro、Hoashi Yurie、Kotani Keisuke、Tatsumoto Shoji、Ishikawa Hiroe、Go Yasuhiro、Inoue Tomio、Mishima Kenji、Akamatsu Wado、Baba Kazuyoshi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 15437-15437

    • DOI

      10.1038/s41598-021-95041-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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] Involvement of the basal nucleus of Meynert on regional cerebral cortical vasodilation associated with masticatory muscle activity in rats.2019

    • Author(s)
      Hotta H, Suzuki H, Inoue T, Stewart M.
    • Journal Title

      J Cereb Blood Flow Metab

      Volume: in press Issue: 12 Pages: 2416-2428

    • DOI

      10.1177/0271678x19895244

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [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] High molecular weight amyloid β1‐42 oligomers induce neurotoxicity via plasma membrane damage2019

    • Author(s)
      Yasumoto Taro、Takamura Yusaku、Tsuji Mayumi、Watanabe‐Nakayama Takahiro、Imamura Keiko、Inoue Haruhisa、Nakamura Shiro、Inoue Tomio、Kimura Atsushi、Yano Satoshi、Nishijo Hisao、Kiuchi Yuji、Teplow David B.、Ono Kenjiro
    • Journal Title

      The FASEB Journal

      Volume: 33 Issue: 8 Pages: 9220-9234

    • DOI

      10.1096/fj.201900604r

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / 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
  • [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] 加齢に伴う口腔機能低下と大脳皮質機能2021

    • Author(s)
      井上富雄
    • Organizer
      日本老年歯科医学会第32回学術大会 「口腔機能の生理的老化と病的老化」シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [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] Electrophysiological maturation and characteristics of human stem cells in sleep bruxism.2021

    • Author(s)
      Avijite KS, Nakamura S, Abe Y, Nakai K, Yasuhara R, Shiga T, Hoashi Y, Kotani K, Inoue T, Mishima K, Akamatsu W, Baba K.
    • Organizer
      The 7th Biennial Joint Congress of JPS-CPS-KAP
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Electrophysiological characterization of sleep bruxism patient-specific induced pluripotent stem cell-derived neurons.2020

    • Author(s)
      Avijite KS, Nakai K, Nakamura S, Yasuhara R, Shiga T, Abe Y, Hoashi Y, Kotani K, Inoue T, Mishima K, Akamatsu W, Baba K.
    • Organizer
      日本顎口腔機能学会第64回学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 睡眠時ブラキシズム患者特異的iPS細胞由来ニューロンの電気生理学的基本特性2020

    • Author(s)
      Avijite Kumer Sarkar,中村史朗,中井健人,小渓啓介,安原理佳,安部友佳,美島健二,井上富雄,馬場一美
    • Organizer
      第67回昭和大学学士会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] ミリセチンは抗酸化作用を介し、ミトコンドリア・細胞膜でアミロイドβオリゴマーによる神経毒性を抑制する2020

    • Author(s)
      木村篤史,森友起子,小口達敬,海野真一,海野麻未,宇高結子,中村史朗,井上富雄,辻まゆみ,小野賢二郎,木内祐二
    • Organizer
      第39回日本認知症学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 高分子Aβオリゴマーは細胞膜完全性を崩壊し細胞毒性を発揮する2020

    • Author(s)
      安本太郎,高村雄策,辻まゆみ,中山隆宏,今村恵子,井上治久,中村史朗,井上富雄,木村篤史,矢野怜,西条寿夫,木内祐二,デービッドテプロフ,小野賢 二郎
    • Organizer
      第39回日本認知症学会学術集会
    • 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] 咀嚼運動制御に関わる神経基盤:脳幹に存在する顎運動制御回路について2020

    • Author(s)
      中村史朗
    • 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] High molecular weight Amyloid b oligomer induces disruption and structural change of cell membrane2020

    • Author(s)
      安本太郎,高村雄策,辻まゆみ,中山隆宏,今村恵子,井上治久,中村史朗,井上富雄,木村篤史,矢野怜,西条寿夫,木内祐二,デービッドテプ ロフ,小野賢二郎
    • Organizer
      第61回日本神経学会学術大会
    • 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] High molecular weight amyloid β1-42 oligomers induce neurotoxicity via plasma membrane damage2020

    • Author(s)
      Yasumoto T, Takamura Y, Tsuji M, Nakayama T, Imamura K, Inoue H, Nakamura S, Inoue T, Kimura AM, Yano S, Nishijo H, Kiuchi Y, Teplow DP, Ono K
    • Organizer
      Alzheimer's Association International Conference
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Vitamin B12 may prevent Aβ oligomer-induced neurotoxicity in Alzheimer's Disease.2020

    • Author(s)
      Kimura AM, Tsuji M, Yasumoto T, Oguchi T, Mori Y, Yano S, Kinnno R, Nakamura S, Inoue T, Teplow DP, Kiuchi Y, Ono K
    • Organizer
      Alzheimer's Association International Conference
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [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] ミリセチンは抗酸化作用を介し、ミトコンドリア・細胞膜でアミロイドβオリゴマーによる神経毒性を抑制する2020

    • Author(s)
      木村篤史,安本太郎,森友起子,小口達敬,海野真一,海野麻未,宇高結子,中村史朗,井上富雄,辻まゆみ,小野賢二郎,木内祐二
    • Organizer
      第363回昭和大学学士会例会
    • Related Report
      2020 Research-status Report
  • [Presentation] Myricetin prevents Aβ oligomer-induced neurotoxicity via cell membrane damage.2020

    • Author(s)
      Kimura A, Yasumoto T, Mori Y, Oguchi T, Nakamura S, Inoue T, Yamada M, Teplow D, Ono K, Kiuchi Y, Tsuji M
    • Organizer
      Advances in Alzheimer’s and Parkinson’s therapies, an AAT-AD/PDTM focus meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [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] Orexin modulates electrophysiological properties of Phox2b neurons located around trigeminal motor nucleus.2019

    • Author(s)
      Nagoya K, Nakamura S, Tsujimura T, Inoue M, Inoue T.
    • Organizer
      Society for Neuroscience 49th annual meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ?Phox2b-expressing neurons located around trigeminal motor nucleus have specific properties for jaw-movements.2019

    • Author(s)
      Nagoya K, Nakamura S, Tsujimura T, Inoue M, 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] Electrophysiological recordings of neurons derived from sleep bruxism patient-specific iPSCs.2019

    • Author(s)
      Nakai K, Shiga T, Abe Y, Hoashi Y, Nakamura S, Yasuhara R, Matsumoto T, Avijite KS, Kotani K, Mishima K, Inoue T, Akamatsu W, Baba K.
    • Organizer
      ISSCR Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Patch-clamp recordings of neurons induced from sleep bruxism patient specific iPSCs.2019

    • Author(s)
      Nakai K, Hoashi Y, Abe Y, Nakamura S, Siga T, Avijite KS, Yasuhara R, Matsumoto T, Kotani K, Inoue T, Mishima K, Akamatsu W, Baba K.
    • Organizer
      97th general session & exhibition of the IADR
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 睡眠時ブラキシズム特異的iPS細胞由来GABA作動性神経細胞の電気生理学的評価2019

    • Author(s)
      中井健人,小溪啓介,帆足有理恵,松本貴志,安部友佳,安原理佳,美島健二,中村史朗,井上富雄,志賀孝宏,赤 松和士,馬場一美
    • Organizer
      日本補綴歯科学会128回学術大会
    • Related Report
      2019 Research-status Report
  • [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
  • [Book] 口腔・顎顔面の機能;有床義歯補綴学2021

    • Author(s)
      井上富雄
    • Total Pages
      344
    • Publisher
      永末書店
    • ISBN
      9784816013836
    • Related Report
      2021 Annual Research Report 2020 Research-status Report
  • [Book] 口腔生理学総論;基礎歯科生理学 第7版2019

    • Author(s)
      井上富雄
    • Total Pages
      475
    • Publisher
      医歯薬出版
    • ISBN
      9784263458464
    • Related Report
      2019 Research-status Report
  • [Book] 咀嚼;基礎歯科生理学 第7版2019

    • Author(s)
      井上富雄、中村史朗
    • Total Pages
      475
    • Publisher
      医歯薬出版
    • ISBN
      9784263458464
    • Related Report
      2019 Research-status Report
  • [Remarks] 昭和大学歯学部口腔生理学講座について

    • URL

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

    • Related Report
      2021 Annual Research Report

URL: 

Published: 2019-07-04   Modified: 2023-01-30  

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