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The roles of sleep in the regulation of the the vascular system of the brain

Research Project

Project/Area Number 20K21456
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 46:Neuroscience and related fields
Research InstitutionUniversity of Tsukuba

Principal Investigator

Hayashi Yu  筑波大学, 国際統合睡眠医科学研究機構, 客員教授 (40525812)

Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords睡眠 / 毛細血管 / 脳血流 / 大脳皮質 / 血流 / マウス / うつ病 / リンパ
Outline of Research at the Start

レム睡眠(夢をよく見る睡眠)の役割はよく分かっていない。これまでの研究の多くは、神経活動やシナプス可塑性など、神経細胞に注目したものであった。本研究では、脳の脈管系に注目した独自のアプローチから、レム睡眠の全く新しい作用の発見に挑む。私たちはこれまでに、睡眠中の大脳毛細管の赤血球の動きを直接観察することに成功した。本研究ではこの技術を活かし、レム睡眠の脳血流の変動とメカニズム、さらには血管以外の脈管系の機能に及ぼす作用の解明に挑む。

Outline of Final Research Achievements

The role of REM (rapid eye movement) sleep is not well understood. In this study, we attempted to uncover effects of REM sleep from approaches focusing on the vascular system of the brain. By establishing a technique to observe the microenvironment in the brain of sleeping mice, we found that during REM sleep, capillary blood flow in the cerebral cortex increases approximately twice as much as during wakefulness in various regions, and that the adenosine receptor A2A is required for this increase in blood flow. We also found that this blood flow elevation is greatly impaired in mouse models of certain diseases. In addition, we established an experimental system to test the possibility that the blood flow elevation that occurs during REM sleep may play an important role in the removal of waste products.

Academic Significance and Societal Importance of the Research Achievements

脳の毛細血管血流は自動調節の機構により安定的なレベルに維持されると考えられているが、我々の研究から、レム睡眠中は他の睡眠覚醒状態とは大きく異なることが判明した。神経細胞の平均発火頻度は覚醒時とレム睡眠とで同程度であることから、neurovascular couplingとは異なる何らかの機構が働くと考えられる。レム睡眠の異常は様々な精神・神経疾患で見られる。本研究成果は、レム睡眠の異常がこうした疾患の悪化に寄与する可能性をも示唆する。従って、異常なレム睡眠を補正する治療は睡眠障害のみならず、精神神経疾患の予防治療の観点からも重要であると考えられ、そうした視点をもたらした点において有意義である。

Report

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

    (17 results)

All 2022 2021 2020 Other

All Journal Article (12 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 11 results,  Open Access: 8 results) Presentation (4 results) (of which Invited: 4 results) Remarks (1 results)

  • [Journal Article] Long-Term Effects of Repeated Social Defeat Stress on Brain Activity during Social Interaction in BALB/c Mice2022

    • Author(s)
      Okamura Hibiki、Yasugaki Shinnosuke、Suzuki-Abe Haruka、Arai Yoshifumi、Sakurai Katsuyasu、Yanagisawa Masashi、Takizawa Hotaka、Hayashi Yu
    • Journal Title

      eNeuro

      Volume: 9 Issue: 3 Pages: ENEURO.0068-22.2022

    • DOI

      10.1523/eneuro.0068-22.2022

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cerebral capillary blood flow upsurge during REM sleep is mediated by A2a receptors2021

    • Author(s)
      Tsai Chia-Jung、Nagata Takeshi、Liu Chih-Yao、Suganuma Takaya、Kanda Takeshi、Miyazaki Takehiro、Liu Kai、Saitoh Tsuyoshi、Nagase Hiroshi、Lazarus Michael、Vogt Kaspar E.、Yanagisawa Masashi、Hayashi Yu
    • Journal Title

      Cell Reports

      Volume: 36 Issue: 7 Pages: 109558-109558

    • DOI

      10.1016/j.celrep.2021.109558

    • NAID

      120007141681

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impaired wakefulness and rapid eye movement sleep in dopamine-deficient mice2021

    • Author(s)
      Kashiwagi Mitsuaki、Kanuka Mika、Tanaka Kaeko、Fujita Masayo、Nakai Ayaka、Tatsuzawa Chika、Kobayashi Kazuto、Ikeda Kazutaka、Hayashi Yu
    • Journal Title

      Molecular Brain

      Volume: 14 Issue: 1 Pages: 170-170

    • DOI

      10.1186/s13041-021-00879-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sleep Architecture in Mice Is Shaped by the Transcription Factor AP-2β2020

    • Author(s)
      Nakai Ayaka、Fujiyama Tomoyuki、Nagata Nanae、Kashiwagi Mitsuaki、Ikkyu Aya、Takagi Marina、Tatsuzawa Chika、Tanaka Kaeko、Kakizaki Miyo、Kanuka Mika、Kawano Taizo、Mizuno Seiya、Sugiyama Fumihiro、Takahashi Satoru、Funato Hiromasa、Sakurai Takeshi、Yanagisawa Masashi、Hayashi Yu
    • Journal Title

      Genetics

      Volume: 216 Issue: 3 Pages: 753-764

    • DOI

      10.1534/genetics.120.303435

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evolutionary Origin of Distinct NREM and REM Sleep2020

    • Author(s)
      Yamazaki Risa、Toda Hirofumi、Libourel Paul-Antoine、Hayashi Yu、Vogt Kaspar E.、Sakurai Takeshi
    • Journal Title

      Frontiers in Psychology

      Volume: 11 Pages: 1-8

    • DOI

      10.3389/fpsyg.2020.567618

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Editorial: The Gating and Maintenance of Sleep and Wake: New Circuits and Insights2020

    • Author(s)
      Lazarus Michael、Hayashi Yu、Honjoh Sakiko、Vogt Kaspar E.、Eban-Rothschild Ada、Liu Qinghua、Sakurai Takeshi
    • Journal Title

      Frontiers in Neuroscience

      Volume: 14 Pages: 1-3

    • DOI

      10.3389/fnins.2020.00773

    • NAID

      120007165426

    • Related Report
      2020 Research-status Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Multimodal nonlinear optical imaging ofCaenorhabditis eleganswith multiplex coherent anti-Stokes Raman scattering, third-harmonic generation, second-harmonic generation, and two-photon excitation fluorescence2020

    • Author(s)
      Miyazaki Shinichi、Leproux Philippe、Couderc Vincent、Hayashi Yu、Kano Hideaki
    • Journal Title

      Applied Physics Express

      Volume: 13 Issue: 7 Pages: 072002-072002

    • DOI

      10.35848/1882-0786/ab9711

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The existence of two states of sleep as a common trait in various animals and its molecular and neuronal mechanisms2020

    • Author(s)
      Kashiwagi Mitsuaki、Hayashi Yu
    • Journal Title

      Current Opinion in Physiology

      Volume: 15 Pages: 197-202

    • DOI

      10.1016/j.cophys.2020.03.007

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Copine-7 Is Required for REM Sleep Regulation Following Cage Change or Water Immersion and Restraint Stress in Mice2020

    • Author(s)
      Chih-Yao Liu, Chia-Jung Tsai, Shinnosuke Yasugaki, Nanae Nagata, Miho Morita, Ayako Isotani, Masashi Yanagisawa, and Yu Hayashi.
    • Journal Title

      Neuroscience Research

      Volume: - Pages: 14-25

    • DOI

      10.1016/j.neures.2020.04.002

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Progressive Changes in Sleep and Its Relations to Amyloid-β Distribution and Learning in Single App Knock-In Mice2020

    • Author(s)
      Maezono Sakura Eri B.、Kanuka Mika、Tatsuzawa Chika、Morita Miho、Kawano Taizo、Kashiwagi Mitsuaki、Nondhalee Pimpimon、Sakaguchi Masanori、Saito Takashi、Saido Takaomi C.、Hayashi Yu
    • Journal Title

      eneuro

      Volume: 7 Issue: 2 Pages: 1-14

    • DOI

      10.1523/eneuro.0093-20.2020

    • NAID

      120007163363

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sleep architecture of adenosine A2A receptor-deficient mice2020

    • Author(s)
      Tsai Chia-Jung, Liu Chih-Yao, Lazarus Michael, Hayashi Yu
    • Journal Title

      Sleep and Biological Rhythms

      Volume: - Issue: 3 Pages: 275-279

    • DOI

      10.1007/s41105-020-00260-2

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Widely Distributed Neurotensinergic Neurons in the Brainstem Regulate NREM Sleep in Mice.2020

    • Author(s)
      Kashiwagi M, Kanuka M, Tatsuzawa C, Suzuki H, Morita M, Tanaka K, Kawano T, Shin JW, Suzuki H, Itohara S, Yanagisawa M, Hayashi Y.
    • Journal Title

      Curr Biol.

      Volume: 30 Issue: 6 Pages: 1002-1010

    • DOI

      10.1016/j.cub.2020.01.047

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Genetic and imaging approaches to elucidate the roles of REM sleep2020

    • Author(s)
      林 悠
    • Organizer
      記憶研究会2020
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 睡眠に注目した新規な脳恒常性維持機構の解明2020

    • Author(s)
      林 悠
    • Organizer
      第93回 日本生化学会大会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] レム睡眠の意義とメカニズム~マウスの遺伝学・イメージングからのアプローチ~2020

    • Author(s)
      林 悠
    • Organizer
      第71回 日本薬理学会北部会次世代薬理学セミナー2020 in 仙台
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Crucial roles for REM sleep in maintaining brain homeostasis as revealed from genetic and imaging approaches2020

    • Author(s)
      林 悠
    • Organizer
      第43回 日本神経科学大会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Remarks] Researchmap

    • URL

      https://researchmap.jp/h-z-k

    • Related Report
      2020 Research-status Report

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Published: 2020-08-03   Modified: 2023-01-30  

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