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Artificial regulation of the sleep-wake state of an experimental animal (rat).

Research Project

Project/Area Number 03557015
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionOsaka Bioscience Institute

Principal Investigator

MATUSMURA Hitoshi  Osaka Bioscience Institute Department of Molecular Behavioral Biology Vice-Head, 第2研究部, 研究副部長 (50173886)

Co-Investigator(Kenkyū-buntansha) OSAKA Toshimasa  Osaka Bioscience Institute Department of Molecular Behavioral Biology Research, 第2研究部, 研究員 (30152101)
TAKAHATA Ryuichi  Osaka Medical College Department of Neuropsychiatry Researcher, 神経精神医学教室, 専攻医 (70247857)
SRI Kantha S  (財)大阪バイオサイエンス研究所, 第2研究部, 研究員
HAYAISHI Osamu  Osaka Bioscience Institute Director, 所長 (40025507)
SRIKANTHA Sachi  Osaka Bioscience Institute Department of Molecular Behavioral Biology Researcher
SRI KANTHA S  (財)大阪バイオサイエンス研究所, 第2研究部, 共同研究員
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 1993: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1992: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1991: ¥7,400,000 (Direct Cost: ¥7,400,000)
KeywordsProstaglandin D_2 / Prostaglandin D synthase / Inorganic selenium compounds / Basal forebrain / Subarachnoid space / Continuous infusion / Microdialysis / Sleep / プロスタグランジンE_2 / リポキシン / ロイコトリエン / セレン / セロトニン / プロスタグランジン / 覚醒 / HMG-CoA還元酵素阻害剤 / ムシモール / 不眠
Research Abstract

The aim of this research project was to develop and establish a method of artificial regulation of the sleepwake state of an experimental animal. This project was important in achieving the ultimate purposes of our study to understand the regulatory mechanism of sleep-wake activities and consciousness and to clarify the meaning of sleep. The results of this project will be useful, as well, in developing a new medicine and/or technique for the treatment of sleep-wake disorders in man.
The results of this research project indicate that, in order to artificially regulate the physiological state of sllep and wakefulness, prostaglandin (PG) D_2 and inhibitors of PGD synthase can be useful probes. When PGD_2 was infused continuously into the subarachnoid space just under the rostal basal forebrain, the slow-wave sleep extraordinarily increased up to the maximum level following a 30-min latency in rats. The sleeping state brought about by PGD_2 was indistinguishable from the natural sleep of the rats. On the other hand, when a PGD-synthase inhibitor, e.g., an inorganic quadrivalent selenium compound, was continuously administered to the rostral basal-forebrain area via a microdialysis probe that had been chronically implanted in the brain, sleep was almost completely suppressed following 2-hours latency. Such extraordinary effects could not obtained in rats with other products in the arachidonate cascade or serotonin and its related compounds, the latter of which have been actively studied for the physiological implication of serotonin in the brain sleep-wake regulatory mechanisms.
Our results also indicate that not only agonists and antagonists but compounds that inhibit the PGD synthase activity also have advantages in designing new drugs of the treatment of sleep-wake disorders.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Hitoshi Matsumura: "Prostagland in D_2-sensitive,sleep-promoting zone defined in the ventral surface of the rostral basal forebrain." The Proceedings of the National Academy of Sciences U.S.A.(In press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shinsuke Satoh: "Promotion of sleep by prostagland in D_2 in rats made isomniac by pretreatment with para-chlorophenylalanine." Neuroscience Research. (In press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Toshimasa Osaka: "Noradrenergic inputs to sleep-related neurons in the preoptic area from the locus coeruleus and the ventrolateral medulla in the rat." Neuroscience Research. 19. 39-50 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Sri Kantha: "Effects of prostaglandin D_2,lipoxins and leukotrienes on sleep and brain temperature of rats." Prostaglandins Leukotrienes and Essential Fatty Acids. 51. 87-93 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ryuichi Takahata: "Intravenous administration of inorganic selenium compounds,inhibitors of prostaglandin D synthase, inhibits sleep in freely moving rats." Brain Research. 623. 65-71 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hitoshi Matsumura: "Inhibition of sleep in rats by inorganic selenium compounds,inhibitors of prostaglandin D synthase." The Proceedings of the National Academy of Sciences U.S.A.88. 9046-9050 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 松村人志(プロスタグランジンと睡眠)(総説): "神経研究の進歩" 医学書院(印刷中), (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 早石修,松村人志(睡眠の分子機構)(総説): "分子神経科学の最先端" 岡田善雄監修,遠山正彌編集,厚生社(印刷中), (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hitoshi Matsumura, Tomoko Nakajima, Toshimasa Osaka, Shinsuke Satoh, Kumiko Kawase, Etsuko Kubo, Sachi Sri Kantha, Keiko Kasahara, Osamu Hayaishi: "Prostaglandin D_2-sensitive, sleep-promoting zone defined in the ventral surface of the rostral basal forebrain." Proc Natl Acad Sci USA. 91 (in press.). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shinsuke Satoh, Hitoshi Matsumura, Tomoko Nakajima, Hirotaka Onoe, Kazuya Sakai, Teruo Nakajima, Michel Jouvet, Osamu Hayaishi: "Promotion of sleep by prostaglandin D_2 in rats made insomniac by pretreatment with para-chlorophenylalanine." Neurosci Res. (in press.). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hitoshi Matsumura: "Prostaglandins and sleep (review)" Shinkei Kenkyu no Shinpo. (in press.). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Toshimasa Osaka, Hitoshi Matsumura: "Noradrenergic inputs to sleep-related neurons in the preoptic area from the locus coeruleus and the ventrolateral medulla in the rat." Neurosci Res. 19. 39-50 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Sri Kantha, H.Matsumura, E.Kubo, K.Kawase, R.Takahata, C.N.Serhan, O.Hayaishi: "Effects of prostaglandin D_2, lipoxins and leukotrienes on sleep and brain temperature of rats." Prostaglandins Leukotrienes and Essential Fatty Acids. 51. 87-93 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ryuichi Takahata, Hitoshi Matsumura, Sachi Sri Kantha, Etsuko Kubo, Kumiko Kawase, Toshiaki Sakai, Osamu Hayaishi: "Intravenous administration of inorganic selenium compounds, inhibitors of prostaglandin D synthase, inhibits sleep in freely moving rats." Brain Res. 623. 65-71 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Osamu Hayaishi, Hitoshi Matsumura, Yoshihiro Urade: "Prostaglandin D synthase is the key enzyme in the promotion of physiological sleep." J Lipid Mediators. 6. 429-431 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hitoshi Matsumura, Ryuichi Takahata, Osamu Hayaishi: "Inhibition of sleep in rats by inorganic selenium compounds, inhibitors of prostaglandin D synthase." Proc Natl Acad Sci USA. 88. 9046-9050 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Matsumura,H.: "Inhibition of sleep in rats by inorganic selenium compounds,inhibitors of prostaglandin D synthase." Proc.Natl.Acad.Sci.USA. 88. 9046-9050 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hayaishi,O.: "Molecular mechanisms of sleep-wake regulation:roles of prostaglandins D_2 and E_2." FASEB(Federation of American Societies for Experimental Biology)Journal. 5. 2575-2581 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] 松村 人志: "睡眠調節とプロスタグランジン(PG)D_2,PGE_2." 日本臨床. 50. 195-201 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takahata,R.: "Intravenous administration of inorganic selenium compounds,inhibitors of prostaglandin D synthase,inhibits sleep in freely moving rats." Brain Res.623. 65-71 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kantha,S.S.: "Effects of prostaglandin D_2,Iipoxins and leukotrienes on sleep and brain temperature of rats."

    • Related Report
      1993 Annual Research Report
  • [Publications] Prostaglandins Leukotrienes and Essential Fatty Acids. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Matsumura,H.: "Site of action for the sleep-promoting,effect of prostaglandin D_2:Examination in freely-behaving rats by bilateral administration using microdialysis techenique." Jpn.J.Psychiatr.Neurol.(Proceeding). (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Matsumura,H.: "Inhibition of sleep in rats by inorganic selenium compounds,inhibitors of prostaglandin D synthase" Proc.Natl.Acad.Sci.USA. 88. 9046-9050 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hayaishi,O.: "Molecular mechanisms of sleep-wake regulation:rolas of prostaglandins D_2 and E_2" FASEB(Federation of American Societies for Experimental Biology)Journal. 5. 2575-2581 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 松村 人志: "睡眠調節とプロスタグランジン(PG)D_2,PGE_2" 日本臨牀. 50. 195-201 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Matsumura,H.: "Sleep inhibiting effect of selenium and its implications in clinical therapy" First IUBMB Conference Biochemistry of Diseases,Abstracts. 166- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Matsumura,H.: "The effects of lovastatin,simvastatin and pravastatin on sleep-wake activity in rats." XI International Symposinm on Drugs Affecting Lipid Metabolism,Abstracts. 76- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Matsumura,H.: "Inhibition of prostaglandin D_2 synthesis may act as a cansative factor of insomnia" Ans-Sleep '92 (International Update Conterenu Fifth Annual Meeting of the Austra lasian sleep Fssociution,Abstraets. 87- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Matsumura,H.: "Inhibition of sleep in rats by inorganic selenium compounds,inhibitors of prostaglandin D synthase" Proc.Natl.Acad.Sci.USA. 88. 9046-9050 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hayaishi,O.: "Molecular mechanisms of sleep-wake regulation:roles of prostaglandins D_2 and E_2" FASEB(Federation of American Societies for Experimental Biology)Journal. 5. 2575-2581 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hayaishi,O.: "Further studies on sleep-wake regulation by prostaglandins D_2 and E_2" Sleep'90. 405-408 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Matsumura,H.: "Sleep inhibiting effect of selenium and its implications in clinical therapy" Abstract of 1st IUBMB Conference Biochemistry of Diseases.

    • Related Report
      1991 Annual Research Report
  • [Publications] Islam,F.: "Inhibition of rat brain prostaglandin D synthase by inorganic selenocompounds" Archiv.Biochem.Biophys.289. 161-166 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 松村 人志: "睡眠調節とプロスタグランジン(PG)D_2,PGE_2" 日本臨牀. 50. 195-201 (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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