Role of histaminergic nervous system in general anesthesia

• Project/Area Number: 17K16753
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: Nakamura Tadaho 東北医科薬科大学, 医学部, 准教授 (80734318)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ヒスタミン神経系 / 吸入麻酔薬 / ヒスタミン / ヒスタミン受容体 / 中枢神経系薬理学 / 神経科学

Outline of Final Research Achievements

Region-specific H1 knock-out mice showed normal in recovery from general anesthesia. On the other hand, astrocyte-specific H1 KO as well as neuron-specific H1 KO had the prolonged recovery status from general anesthesia.

Academic Significance and Societal Importance of the Research Achievements

社会の高齢化に伴い高齢の手術麻酔患者が増加している。術後認知機能障害は高齢患者の主要な術後合併症の一つである。本研究の結果から、吸入全身麻酔薬からの覚醒には神経細胞だけでなくアストロサイトに発現するH1受容体が関与していることが示唆された。これまでの研究でヒスタミン神経系による認知記憶機能の制御が明らかになっているので、部位特異的なアプローチだけでなく細胞特異的なH1受容体へのアプローチが、全身麻酔からの回復を促進しその後の認知記憶機能障害を予防するため研究基盤になる可能性があると考られる。

Research Products

• [Journal Article] Brain histamine H1 receptor occupancy after oral administration of desloratadine and loratadine (2019)
  • Author(s): Nakamura Tadaho、Hiraoka Kotaro、Harada Ryuichi、Matsuzawa Takuro、Ishikawa Yoichi、Funaki Yoshihito、Yoshikawa Takeo、Tashiro Manabu、Yanai Kazuhiko、Okamura Nobuyuki
  • Journal Title: Pharmacology Research & Perspectives Volume: 7 Issue: 4
  • DOI: 10.1002/prp2.499
  • Peer Reviewed / Open Access
• [Journal Article] Intraoperative hemorrhage in revision total hip arthroplasty: a retrospective single-center study (2019)
  • Author(s): Saito Kana、Kaiho Yu、Tamii Toru、Nakamura Tadaho、Kameyama Eri、Yamauchi Masanori
  • Journal Title: Journal of Anesthesia Volume: 33 Issue: 3 Pages: 399-407
  • DOI: 10.1007/s00540-019-02644-2
  • NAID: 40021917708
  • Peer Reviewed / Open Access
• [Journal Article] Histamine N-methyltransferase regulates aggression and the sleep-wake cycle (2017)
  • Author(s): Naganuma Fumito、Nakamura Tadaho、Yoshikawa Takeo、Iida Tomomitsu、Miura Yamato、Karpati Aniko、Matsuzawa Takuro、Yanai Atushi、Mogi Asuka、Mochizuki Takatoshi、Okamura Nobuyuki、Yanai Kazuhiko
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 15899-15899
  • DOI: 10.1038/s41598-017-16019-8
  • Peer Reviewed / Open Access
• [Presentation] ヒスタミン神経細胞の薬理遺伝学的活性化が睡眠覚醒に及ぼす影響 (2020)
  • Author(s): 中村正帆、長沼史登、黒柳浩志、田中聖人、吉川雄朗、谷内一彦、岡村信行
  • Organizer: 第22回日本ヒスタミン学会
• [Presentation] Histamine N-Methyltransferase in the Brain. (2019)
  • Author(s): T Yoshikawa, T Nakamura, K Yanai
  • Organizer: 48th Meeting of the European Histamine Research Society
  • Int'l Joint Research / Invited
• [Presentation] BEHAVIORAL CAHNGES RELATED TO INCREASED BRAIN HISTAMINE (2019)
  • Author(s): T Nakamura, F Naganuma, T Yoshikawa, N Okamura and K Yanai
  • Organizer: Novel Pain Therapeutics: from Basic Research to Clinical Translation and Rehabilitation.
  • Int'l Joint Research
• [Presentation] Histamine H1 receptor occupancy measured by PET in the human brain after oral administration of desloratadine (2019)
  • Author(s): T Nakamura, T Yoshikawa, M Tashiro, N Okamura, K Yanai
  • Organizer: 48th Meeting of the European Histamine Research Society
  • Int'l Joint Research
• [Presentation] 経口デスロラタジンの脳内ヒスタミン H1受容体結合：陽電子放出断層撮影を用いたin vivoランダム割付二重盲検クロスオーバー臨床試験 (2019)
  • Author(s): 中村正帆、平岡宏太良、原田龍一、松澤拓郎、吉川雄朗、長沼史登、田代学、谷内一彦、岡村信行
  • Organizer: 第40回日本臨床薬理学会
• [Presentation] 中枢ヒスタミン神経細胞の急性刺激はマウス攻撃行動を惹起する (2019)
  • Author(s): 黒柳浩志、田中聖人、長沼史登、中村正帆、岡村 信行
  • Organizer: 第70回日本薬理学会北部会
• [Presentation] The Role of Histamine H1 Receptors in Loss of Consciousness induced by Sevoflurane. (2018)
  • Author(s): Toru Tamii, Tadaho Nakamura, Masanori Yamauchi, Takeo Yoshikawa, Kazuhiko Yanai
  • Organizer: ANESTHESIOLOGY2018 Annual Meeting of American Society of Anesthesiologists
  • Int'l Joint Research
• [Presentation] H1 receptor deletion facilitates loss of consciousness induced by inhaled general anesthetics. (2018)
  • Author(s): Toru Tamii, Tadaho Nakamura, Fumito Naganuma, Takeo Yoshikawa, Nobuyuki Okamura, Kazuhiko Yanai
  • Organizer: World Histamine Symposium 2018, A satellite symposium of WCP2018, 2nd Joint Symposium of European and Japanese Histamine Research Societies
  • Int'l Joint Research
• [Presentation] HISTAMINE CLEARANCE THROUGH POLYSPECIFIC TRASNPORTERS AND HISTAMINE N-METHYLTRANSFERASE IN THE BRAIN (2018)
  • Author(s): Tadaho Nakamura, Takeo Yoshikawa, Kazuhiko Yanai
  • Organizer: World Histamine Symposium 2018, A satellite symposium of WCP2018, 2nd Joint Symposium of European and Japanese Histamine Research Societies
  • Int'l Joint Research
• [Presentation] THE EFFECT OF H3 RECEPTOR ANTAGONIST ON NEUROPATHIC PAIN (2017)
  • Author(s): Tadaho Nakamura, Takuro Matsuzawa, Maria Mogilevskaya, Asuka Mogi, Takeo Yoshikawa, Fumito Naganuma, Nobuyuki Okamura and Kazuhiko Yanai
  • Organizer: Histamine 2017 1st Joint meeting of the European and Japanese Histamine Research Societies
  • Int'l Joint Research
• [Presentation] ヒスタミンNメチルトランスフェラーゼのin vivo機能解析 (2017)
  • Author(s): 中村正帆、吉川雄朗、岡村 信行
  • Organizer: 第68回日本薬理学会北部会
• [Presentation] Role of Histamine Receptors in Desflurane Anesthesia (2017)
  • Author(s): Toru Tamii, Tadaho Nakamura, Masanori Yamauchi, Takeo Yoshikawa, Kazuhiko Yanai
  • Organizer: ANESTHESIOLOGY2017 Annual Meeting of American Society of Anesthesiologists
  • Int'l Joint Research