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Studies of neurophysiological regulation of sleep-wake states using animal models for sleep research

Research Project

Project/Area Number 18603002
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 睡眠学
Research InstitutionTokyo Medical and Dental University

Principal Investigator

HONDA Kazuki  Tokyo Medical and Dental University, Institute of Biomaterials and Bioengineering, Professor (70173656)

Co-Investigator(Kenkyū-buntansha) HIRAI Keiji  Tokyo Medical and Dental University, 難治疾患研究所, 准教授 (70156628)
片山 芳文  東京医科歯科大学, 難治疾患研究所, 教授 (20014144)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsSleep disorder / Non-REM sleep / REM sleep / Food intake / Motilin / Ghrelin / Orexin / Parkinson's Disease / ドパミン / ナルコレプシー / オレキシン / ドーパミン
Research Abstract

In recent decades, many of the chemical and neuronal substrates involved in sleep-wake regulation have been identified. Recently, orexins A and B involved in the regulation of the feeding and arousal states, were identified. An intracerebroventricular (icv) infusion of both orexins A and B has been observed to induce arousal effects in rats. In the present studies, we investigated the involvement of humoral factors in neurophysiological regulation of sleep-wake states and animal models for sleep research.
1. An icv infusion of orexin A for a 5-h period markedly increased the amount of wakefulness over the baseline value. OX2R antagonist decreased orexin A-induced wakefulness. Although OX2R antagonist treatment alone slightly changed each sleep parameter, no significant difference was observed. Pretreatment with OX2R antagonist, significant inhibited orexin A-induced wakefulness in rats. The finding this study therefore suggest that OX2R involved in arousal state regulation.
2. Motilin is known to regulate the feeding system. We investigated the effects of icv infusion of motilin (1, 10, 50, 100 nml) on the sleep-waking cycle in the freely behaving rats. Motilin at the dose of 100 nmol markedly increased the amount of wakefulness by 75.0% (p<0.05) over the baseline value. These finding suggest that motilin also modulates sleep-wake states and behavioral responses.
3. Parkinson's Disease (PD) is a progressive neurodegenerative disease wherein dopaminergic neuron in the substantia nigra pars compacta (SNpc) are destroyed. In this study, α-synuclein transgenic (TG) mice for the diminished expression of dopaminergic neurons in SNpc were used to investigate sleep architecture, and compared to wild type (WT) mice. Analysis of sleep architecture had no significant differences between TG and WT mice. Further research on the influence of the dopaminergic system on the sleep-wake cycle using PD models is needed to validate the observed sleep-wake cycle disturbances.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (19 results)

All 2007 2006

All Journal Article (11 results) (of which Peer Reviewed: 4 results) Presentation (4 results) Book (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Sensory stimulation triggering spindles during sleep stage 22007

    • Author(s)
      Sato Y, Fukuoka Y, Minamitani H, Honda K.
    • Journal Title

      SLEEP 30

      Pages: 511-518

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 睡眠のメカニズムとその生理機能2007

    • Author(s)
      本多和樹
    • Journal Title

      システム・情報部門学術講演会2007講演論文集

      Pages: 19-24

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Sensory stimulation triggering spindles during sleep stage 22007

    • Author(s)
      Sato Y, Fukuoka Y, Minanzitani H, Honda K.
    • Journal Title

      SLEEP 30

      Pages: 511-518

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A histamine. synthesis inhibitor, alpha-fluoromethyl histidine, inhibits orexin-induced wakefulness in rats2007

    • Author(s)
      Honda K, Seki Y, Kotani M, Akanmu MA, Hirai K, Katayama Y, Yanai K
    • Journal Title

      J Sleep Res 15(supple 1)

      Pages: 140-141

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Sensory stimulation triggering spindles during sleep stage 2.2007

    • Author(s)
      Sato Y, Fukuoka Y, Minamitan i H, Honda K.
    • Journal Title

      SLEEP 30

      Pages: 511-518

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 睡眠研究と動物モデル2007

    • Author(s)
      本多和樹
    • Journal Title

      日本薬理学雑誌 129

      Pages: 413-417

    • NAID

      10019727646

    • Related Report
      2007 Annual Research Report
  • [Journal Article] A histamine synthesis inhibitor, alpha-fluoromethyl histidine, inhibit s orexin-induced wakefulness in rats2006

    • Author(s)
      Honda K, Seki Y, Kotani M, Akanmu MA, Hirai K, Katayama Y, Yanai K.
    • Journal Title

      J Sleep Res 15(Supple1)

      Pages: 140-141

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A histamine synthesis inhibitor, alpha-fluoromethy1 histidine, inhibits orexin-induced wakefulness in rats2006

    • Author(s)
      Honda K, Seki Y, Kotani M, Akanmu MA, Hirai K, Katayama Y, Yanai K.
    • Journal Title

      J Sleep Res 15(Supple.1)

      Pages: 140-141

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effects of neuropeptide-Y Y2-receptor agonist, PYY3-36 on sleep-wak cycle in rats.2006

    • Author(s)
      Honda K, Ukpomwan OE, Katayama Y, Akanmu MA
    • Journal Title

      J Sleep Res 15(Supple.1)

      Pages: 140-140

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Brain-gut peptides involved in the regulation of sleep and feeding : their actions in the enteric nervous system of the guinea-pig ileum2006

    • Author(s)
      Katayama Y, Honda K
    • Journal Title

      J Sleep Res 15(Supple.1)

      Pages: 235-235

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 液性因子による睡眠覚醒制御2006

    • Author(s)
      本多和樹
    • Journal Title

      神経内科 64

      Pages: 225-232

    • Related Report
      2006 Annual Research Report
  • [Presentation] 睡眠のメカニズムとその生理機能2007

    • Author(s)
      本多和樹
    • Organizer
      計測自動制御学会 システム・情報部門学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-26
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] A histamine synthesis inhibitor, alpha-fluoromethyl histidine, inhibits orexin-induced wakefulness in rats2006

    • Author(s)
      Honda K, Seki Y, Kotani M, Akanmu MA, Hirai K, Katayama Y, Yanai K.
    • Organizer
      18th Cong Eur Sleep Res Soc
    • Place of Presentation
      Innsubruck
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Effects of neuropeptide-Y Y2-receptor agonist, PYY3-36 on sleep-wake cycle in rats2006

    • Author(s)
      Honda K, Ukpomwan OE, Katayama Y, Akanmu MA.
    • Organizer
      18th Cong Eur Sleep Res Soc
    • Place of Presentation
      Innsubruck
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Brain-gut peptides involved in the regulation of sleep and feeding : their actions in the enteric nervous system of the guinea-pig ileum2006

    • Author(s)
      Katayama Y, Honda K.
    • Organizer
      18th Cong Eur Sleep Res Soc
    • Place of Presentation
      Innsubruck
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 眠りの科学とその応用 -睡眠のセンシング技術と良質な睡眠の確保に向けての研究開発-, 本多和樹監修2007

    • Author(s)
      本多和樹
    • Total Pages
      331
    • Publisher
      シーエムシー出版
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Book] 睡眠とメンタルヘルス-睡眠科学への理解を深める-2006

    • Author(s)
      本多和樹
    • Total Pages
      21
    • Publisher
      ゆまに書房、東京
    • Related Report
      2006 Annual Research Report
  • [Patent(Industrial Property Rights)] 睡眠導入剤、並びに、これを含有する医薬組成物及び食品2007

    • Inventor(s)
      大崎愛弓 本多和樹
    • Industrial Property Rights Holder
      東京医科歯科大学
    • Filing Date
      2007-07-21
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 睡眠導入剤、並びに、これを含有する医薬組成物及び食品2007

    • Inventor(s)
      大崎愛弓本多和樹
    • Industrial Property Rights Holder
      東京医科歯科大学
    • Filing Date
      2007-07-21
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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