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Role of the hypothalamus in dyspnea perception: a basic study to develop the methods for relieving dyspnea

Research Project

Project/Area Number 20K19474
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 59010:Rehabilitation science-related
Research InstitutionAomori University of Health and Welfare (2022-2023)
Uekusa Gakuen University (2020-2021)

Principal Investigator

Fukushi Isato  青森県立保健大学, 健康科学部, 講師 (20738497)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords視床下部 / 呼吸困難感 / 呼吸リズム / オレキシン / 摘出間脳下部脳幹脊髄標本 / 運動指令随伴発射
Outline of Research at the Start

呼吸困難感は呼吸を行うことが容易ではないという感覚,あるいは呼吸に伴う不快感・苦痛をいう.呼吸困難感は患者の活動量を低下させ,ひいてはQOL低下を引き起こす要因となるため,患者の呼吸困難感を軽減させることは,呼吸リハビリテーション実施上,極めて重要である.本研究は,未だ解明されていない呼吸困難感の知覚機序を明らかにすることを究極の目的としつつ,その一環として,呼吸困難感知覚において視床下部が果たす役割の解明を目指している.

Outline of Final Research Achievements

Mitigating dyspnea in patients with respiratory diseases is crucial in clinical settings. However, the mechanisms underlying dyspnea perception remain largely unexplored. We hypothesized the existence of a respiratory feedback control system wherein dyspnea is perceived through the transmission of ascending copy information regarding respiratory motor output from the lower brainstem to the higher brain via the hypothalamus. Furthermore, we proposed that perceived dyspnea enhances the neural drives of hypothalamic neurons to the lower brainstem. Our study demonstrated the presence of ascending neural signals corresponding to the respiratory motor output copy information from the brainstem respiratory center, identified as the motor command corollary discharge. We also identified an area in the hypothalamus exhibiting respiration-synchronized rhythmic activity and established its anatomical connection with the respiratory center in the medulla. These findings support our hypothesis.

Academic Significance and Societal Importance of the Research Achievements

呼吸困難感とは,呼吸を行うことが容易ではないという感覚,あるいは呼吸に伴う不快感・苦痛をいう.慢性閉塞性肺疾患,肺線維症などの呼吸器疾患に罹患した患者は,労作時に体内酸素レベルが低下し,呼吸困難感を知覚することが少なくない.呼吸困難感は患者の活動量を低下させ,ひいてはQOL低下を引き起こす要因となるため,患者の呼吸困難感を軽減させることは,呼吸リハビリテーション実施上,極めて重要である.しかし,現時点で呼吸困難感の知覚機序は十分には解明されておらず,その緩和法も確立されていない.本研究成果は,呼吸困難感の知覚機序解明に寄与し,呼吸困難感の緩和法開発に寄与するものと期待される.

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (24 results)

All 2024 2022 2021 2020

All Journal Article (8 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Presentation (14 results) (of which Int'l Joint Research: 5 results) Book (2 results)

  • [Journal Article] Dual orexin receptor blocker suvorexant attenuates hypercapnic ventilatory augmentation in mice2022

    • Author(s)
      Fukushi Isato、Yokota Shigefumi、Takeda Kotaro、Terada Jiro、Umeda Akira、Yoshizawa Masashi、Kono Yosuke、Hasebe Yohei、Onimaru Hiroshi、Pokorski Mieczyslaw、Okada Yasumasa
    • Journal Title

      Brain Research

      Volume: 1795 Pages: 148061-148061

    • DOI

      10.1016/j.brainres.2022.148061

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of microglia in blood pressure and respiratory responses to acute hypoxic exposure in rats2022

    • Author(s)
      Yoshizawa Masashi、Fukushi Isato、Takeda Kotaro、Kono Yosuke、Hasebe Yohei、Koizumi Keiichi、Ikeda Keiko、Pokorski Mieczyslaw、Toda Takako、Okada Yasumasa
    • Journal Title

      The Journal of Physiological Sciences

      Volume: 72 Issue: 1 Pages: 1-13

    • DOI

      10.1186/s12576-022-00848-y

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of wearing facemasks on the sensation of exertional dyspnea and exercise capacity in healthy subjects2021

    • Author(s)
      Fukushi Isato、Nakamura Masatoshi、Kuwana Shun-ichi
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 9 Pages: e0258104-e0258104

    • DOI

      10.1371/journal.pone.0258104

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation of Astrocytes in the Persistence of Post-hypoxic Respiratory Augmentation2021

    • Author(s)
      Fukushi Isato、Takeda Kotaro、Pokorski Mieczyslaw、Kono Yosuke、Yoshizawa Masashi、Hasebe Yohei、Nakao Akito、Mori Yasuo、Onimaru Hiroshi、Okada Yasumasa
    • Journal Title

      Frontiers in Physiology

      Volume: 12 Pages: 757731-757731

    • DOI

      10.3389/fphys.2021.757731

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mechanisms underlying the sensation of dyspnea2021

    • Author(s)
      Fukushi Isato、Pokorski Mieczyslaw、Okada Yasumasa
    • Journal Title

      Respiratory Investigation

      Volume: 59 Issue: 1 Pages: 66-80

    • DOI

      10.1016/j.resinv.2020.10.007

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Calcium Imaging Analysis of Cellular Responses to Hypercapnia and Hypoxia in the NTS of Newborn Rat Brainstem Preparation2021

    • Author(s)
      Hiroshi Onimaru, Itaru Yazawa, Kotaro Takeda, Isato Fukushi and Yasumasa Okada
    • Journal Title

      Front. Physiol.

      Volume: 12 Pages: 1-11

    • DOI

      10.3389/fphys.2021.645904

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] O2-Dependent Protein Internalization Underlies Astrocytic Sensing of Acute Hypoxia by Restricting Multimodal TRPA1 Channel Responses2020

    • Author(s)
      Uchiyama Makoto、Nakao Akito、Kurita Yuki、Fukushi Isato、Takeda Kotaro、Numata Tomohiro、Tran Ha Nam、Sawamura Seishiro、Ebert Maximilian、Kurokawa Tatsuki、Sakaguchi Reiko、Stokes Alexander J.、Takahashi Nobuaki、Okada Yasumasa、Mori Yasuo
    • Journal Title

      Current Biology

      Volume: 30 Issue: 17 Pages: 3378-3396

    • DOI

      10.1016/j.cub.2020.06.047

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural and functional connectivity from the dorsomedial hypothalamus to the ventral medulla as a chronological amplifier of sympathetic outflow.2020

    • Author(s)
      Kono Y, Yokota S, Fukushi I, Arima Y, Onimaru H, Okazaki S, Takeda K, Yazawa I, Yoshizawa M, Hasebe Y, Koizumi K, Pokorski M, Toda T, Sugita K, Okada Y.
    • Journal Title

      Sci Rep.

      Volume: 10 Issue: 1 Pages: 13325-13325

    • DOI

      10.1038/s41598-020-70234-4

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Effects of a Dual Orexin Receptor Blocker Suvorexant on Ventilatory Control2022

    • Author(s)
      Isato Fukushi, Shigefumi Yokota, Kotaro Takeda, Jiro Terada, Akira Umeda, Masashi Yoshizawa, Yosuke Kono, Yohei Hasebe, Hiroshi Onimaru, Mieczyslaw Pokorski, Yasumasa Okada
    • Organizer
      The 45th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2022 Research-status Report
  • [Presentation] Blockade of orexin receptors inhibits hypercapnic ventilatory augmentation in mice2022

    • Author(s)
      Isato Fukushi, Shigefumi Yokota, Kotaro Takeda, Jiro Terada, Akira Umeda, Masashi Yoshizawa, Yosuke Kono, Yohei Hasebe, Hiroshi Onimaru, Mieczyslaw Pokorski, Yasumasa Okada
    • Organizer
      The 8th Japanese society of respiratory Physical Therapy
    • Related Report
      2022 Research-status Report
  • [Presentation] Hypothalamic respiration-synchronized rhythmic activity in the diencephalon-lower brainstem-spinal cord preparation2022

    • Author(s)
      Isato Fukushi, Yosuke Kono, Shigefumi Yokota, Kotaro Takeda, Masashi Yoshizawa, Yohei Hasebe, Mieczyslaw Pokorski, Yasumasa Okada
    • Organizer
      The 15th Oxford Breathing Meeting
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Astrocytes are involved in the maintenance of respiratory augmentation in the post-hypoxic recovery phase2021

    • Author(s)
      Fukushi Isato、Takeda Kotaro、Yoshizawa Masashi、Kono Yosuke、Hasebe Yohei、Onimaru Hiroshi、Okada Yasumasa
    • Organizer
      The 7th Japanese society of respiratory Physical Therapy
    • Related Report
      2021 Research-status Report
  • [Presentation] アストロサイトは低酸素負荷後の呼吸増強を持続させる2021

    • Author(s)
      福士勇人, 武田湖太郎, Pokorski Mieczyslaw, 横田茂文, 岡田泰昌
    • Organizer
      第126回日本解剖学会総会・全国学術集会・第98回日本生理学会合同大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Astrocytes mediate the post-hypoxic persistent respiratory augmentation2021

    • Author(s)
      Fukushi I, Takeda K, Pokorski M, Kono Y, Yoshizawa M, Hasebe Y, Nakao A, Mori Y, Onimaru H, Okada Y
    • Organizer
      Experimental Biology 2021 Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Microglial Involvement in Stress‐induced Prolonged Sympathetic Nervous Excitation in Rats2020

    • Author(s)
      Yoshizawa M, Fukushi I, Takeda K, Kono Y, Hasebe Y, Koizumi K, Toda T, Okada Y
    • Organizer
      Experimental Biology 2020 Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Role of Microglia in Ventilatory and Blood Pressure Responses to Acute Hypoxia2020

    • Author(s)
      Okada Y, Yoshizawa M, Fukushi I, Takeda K, Kono Y, Hasebe Y, Koizumi K, Toda T
    • Organizer
      Experimental Biology 2020 Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Astrocytes play an active role in persistence of respiratory augmentation in the recovery phase after hypoxic exposure2020

    • Author(s)
      Fukushi I, Kono Y, Takeda K, Yokota S, Onimaru H, Pokorski M, Okada Y
    • Organizer
      Experimental Biology 2020 Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Role of microglia in sustenance of stress-induced sympathetic excitation in rats2020

    • Author(s)
      Yoshizawa M, Fukushi I, Takeda K, Kono Y, Hasebe Y, Koizumi K, Toda T, Okada Y
    • Organizer
      The 43rd Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2020 Research-status Report
  • [Presentation] Calcium imaging analysis of cellular responses to hypercapnia and hypoxia in the NTS of newborn rat brainstem preparation2020

    • Author(s)
      Onimaru H, Yazawa I, Fukushi I, Takeda K, Okada Y
    • Organizer
      The 43rd Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2020 Research-status Report
  • [Presentation] Astrocytic activation is necessary for post-hypoxic persistent respiratory augmentation2020

    • Author(s)
      Fukushi I, Takeda K, Pokorski M, Yazawa I, Okazaki S, Kono Y, Yoshizawa M, Yokota S, Onimaru H, Okada Y
    • Organizer
      The 43rd Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2020 Research-status Report
  • [Presentation] Suppression of hypercapnic ventilatory response by suvorexant (Belsomra (R))2020

    • Author(s)
      Fukushi I, Yokota S, Takeda K, Terada J, Okada Y
    • Organizer
      The 60th Annual Meeting of the Japanese Respiratory Society
    • Related Report
      2020 Research-status Report
  • [Presentation] ストレス刺激による循環応答におけるマイクログリアの関与2020

    • Author(s)
      吉沢雅史, 福士勇人, 河野洋介, 長谷部洋平, 小泉敬一, 武田湖太郎, 岡田泰昌, 戸田孝子
    • Organizer
      第54回小児循環器学会総会・学術集会
    • Related Report
      2020 Research-status Report
  • [Book] Vitamins and Hormones Volume 1272024

    • Author(s)
      Isato Fukushi, Shigefumi Yokota, Hasebe Yohei, Mieczyslaw Pokorski, Yasumasa Okada
    • Publisher
      Elsevier
    • Related Report
      2023 Annual Research Report
  • [Book] Structure-Function Relationships in Various Respiratory Systems2020

    • Author(s)
      Okada Yasumasa、Yokota Shigefumi、Fukushi Isato
    • Total Pages
      294
    • Publisher
      Springer
    • ISBN
      9789811555961
    • Related Report
      2020 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2025-01-30  

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