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Molecular biological study of sleep-wake regulating mechanisms and its clinical implication

Research Project

Project/Area Number 06508003
Research Category

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

Allocation TypeSingle-year Grants
Research Field Functional biochemistry
Research InstitutionOsaka Bioscience Institute

Principal Investigator

HAYAISHI Osamu  Osaka Bioscience Institute, Director, 所長 (40025507)

Co-Investigator(Kenkyū-buntansha) OSAKA Toshimasa  Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Research, 第2研究部, 研究員 (30152101)
WATANABE Kikuko  Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Research, 第2研究部, 研究員 (90211672)
URADE Yoshihiro  Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Vice-Hea, 第2研究部, 研究副部長 (10201360)
MATSUMURA Hitoshi  Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Vice-Hea, 第2研究部, 研究副部長 (50173886)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥49,900,000 (Direct Cost: ¥49,900,000)
Fiscal Year 1995: ¥16,200,000 (Direct Cost: ¥16,200,000)
Fiscal Year 1994: ¥33,700,000 (Direct Cost: ¥33,700,000)
KeywordsProstaglandin D_2 / Prostaglandin E_2 / Sleep-wake activities / A_2-adenosine receptor / Rostral basal forebrain / Cerebrospinal fluid / beta-Trace protein / Prostaglandin D synthase / プロスタグランジンD合成酵素 / 脈絡叢 / クモ膜 / 軟膜
Research Abstract

Our research group found the sleep-promoting effect of prostaglandin (PG) D_2 and the awaking effect of PGE_2. The mechanisms underlying these effects have been studied in the present research project. We showed by use of in situ hybridization and immunocytochemical techniques that the brain PGD synthase, the enzyme responsible for the synthesis of PGD_2 in the brain, is abundantly expressed in the leptomeninges covering the surface of the brain, as well as choroid plexus, where cerebrospinal fluid (CSF) is produced. Interestingly, the beta-trace protein, the second most abundant protein in the human CSF,was identified as the brain PGD synthase, in the collaborative studies with foreign research groups. The site of action for the sleep-promoting effect of PGD_2 had been postulated to be located in the preoptic area, a sleep center ; however, our recent experimental results clearly showed that the real site of action is located in the ventral surface of a basal-forebrain region located rostral to the preoptic area. This basal-forebrain region includes ventral striatum, i.e., the accumbens nucleus and the olfactory tubercle. We also demonstrated that the concentration of PGD_2 in the CSF of the rat was higher during the daytime, the sleeping period of the animal, than during the night. Thus, it is postulated that PGD_2 synthesized in the membrane tissues underlying the ventral surface of the rostral basal forebrain acts at the surface layr of the brain region to initiate sleep. The signal produced by PGD_2 may be transmitted to neural circuits responsible for the sleep-wake regulation. In the process, A_<2a>-adenosine receptors abundantly expressed in the ventral striatum are inferred to be crucially involved, because CGS21680, an A_<2a>-adenosine agonist, markedly promoted sleep when administered to the same region, whereas KF17837, an A_2-adenosine antagonist, inhibited the sleep promotion produced by PGD_2.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Haushila P Pandey: "Circadian variations of prostaglandins D_2, E_2, and F_<2α> in the cerebrospinal fluid of anesthetixzed rats." Biochem Biophys Res Commun. 213. 625-629 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshihiro Urade: "Structural and functional signifizance of Cysteine residues of Glutathione-independent prostaglandin D synthase" J Biol Chem. 270. 1422-1428 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshihiro Urade: "Prostaglandin D, E, and F synthases" J Lipid Mediators Cell Signalling. 12. 257-273 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hitoshi Matsumura: "Prostaglandin D_2-sensitive,sleep-promoting zone defined in the ventral surface of the rostral basal forebrain." Proc Natl Acad Sci USA. 91. 11998-12002 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kikuko Watanabe: "Identification of β-trace as prostaglandin D synthase" Biochem Biophys Res Commun. 203. 1110-1116 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shinsuke Satoh: "Promotion of sleep mediated by the A_<2α>-adenosione receptor and possible involve of this receptor in the sleep induced by prostaglandin d_2 in rats." Proc Natl Acad Sci USA. (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hitoshi Matsumura, Tomoko Nakajima, et al.: "Prostaglandin D_2-sensitive, sleep-promoting zone defined in the ventral furface of the rostral basal forebrain" Proc Natl Acad Sci USA. 91. 11998-12002 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Haushila P Pandey, Arjun Ram, Hitoshi Matsumura, et al.: "Circadian variations of prostaglandins D_2, E_2, and F_<2alpha> in the cerebrospinal fluid of anesthetized rats" Biochem Biophys Res Commun. 213. 625-629 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Haushila P Pandey, Arjun Ram, Hitoshi Matsumura, et al.: "Concentration of prostaglandin D_2 in cerebrospinal fluid exhibits a circadian alteration in consciousrats" Biochem Mol Biol Internat. 37. 431-437 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shinsuke Satoh, Hitoshi Matsumura, et al.: "Promotion of sleep mediated by the A_<2a>-adenosine receptor and possible involvement of this receptor in the sleep induced by prostaglandin D_2 in rats" Proc Natl Acad Sci USA. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shinsuke Satoh, Hitoshi Matsumura, et al.: "Promotion of sleep by prostaglandin D_2 in rats made insomniac by pretreatment with para-chlorophenylalanine" Neurosci Res. 21. 41-50 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kikuko Watanabe, Yoshihiro Urade, et al.: "Identification of beta-trace as prostaglandin D synthase" Biochem Biophys Res Commun. 203. 1110-1116 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshihiro Urade, Toshiki Tanaka, Naomi Eguchi, et al.: "Structural and functional significance of Cysteine residues of Glutathione-independent prostaglandin D synthase" J Biol Chem. 270. 1422-1428 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tohimasa 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
      1995 Final Research Report Summary
  • [Publications] Toshimasa Osaka, Hitoshi Matsumura: "Noradrenaline inhibits preoptic sleep-active neurons through alpha_2-receptors in the rat" Neurosci Res. 21. 323-330 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Marie-Francoise Vesin, Yoshihiro Urade, et al.: "Neuronal and glial prostaglandin D synthase isozymes in chick dorsal root ganglia : a light and electron microscopic immunocytochemical study" J Neurosci. 15. 470-476 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Dmitry Gerashchenko, Hitoshi Matsumura: "Continuous recordings of brain regional circulation during sleep/wake state transitions in rats" Am J Physiol 270 (Regulatory Integrative Comp Physiol 39). (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hitoshi Matsumura: "Prostaglandin D_2-sensitive, sleep-promopting zone defined in the ventral surface of the rostral basal forebrain." Proc Natl Acad Sci USA. 91. 11998-12002 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshihiro Urade: "Structural and functional significance of cysteins residues of glutathione-independent prostaglandin D synthase." J Biol Chem. 270. 1422-1428 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Haushila P Pandey: "Circadian variations of prostaglandins D_2, E_2, and F_<2α> in the cerebrospinal fluid of anesthetized rats." Biochem Biophys Res Commun. 213. 625-629 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Haushila P Pandey: "Concentration of prostaglandin D_2 in cerebrospinal fluid exhibits a circadian alteration in conscious rats." Biochem Mol Biol Internat. 37. 431-437 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Marie-Francoise Vesin: "Neuronal and glial prostaglandin D synthase isozymes in chick dorsal root ganglia: a light and electron microscopic immunocytochemical study." J Neurosci. 15. 470-476 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shinsuke Satoh: "Promotion of sleep mediated by the A_<2a>-adenosine receptor and possible involvement of this receptor in the sleep induced by prostaglandin D_2 in rats." Proc Natl Acad Sci USA. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Toshimasa Osaka: "Noradrenergic inpurtsto sleep-related neurons in the preoptic area from the locus coeruleus and the ventrolateral medulla in the rat" Neuroscience Research. 19. 39-50 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hitoshi Matsumura: "Prostaglandin D_2-sensitive,sleep-promoting zone defined in the ventral surface of the rostral basal forebrain" Proc.Natl.Acad.Sci.USA. 91. 11998-12002 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shinsuke Satoh: "Promotion of sleep by prostaglandin D_2 in rats made insomniac by pretreatment with para-chlorophenylalanine" Neuroscience Research. 21. 41-50 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kikuko Watanabe: "Identification of β-trace as prostaglandin D-synthase" Biochem.Biophys.Res.Commun.203. 1110-1116 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshihiro Urade: "Structural and functional significance of Cysteine residues of Glutathione-independent prostaglandin D synthase" Journal of Biological Chemistry. 270. 1422-1428 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshihiro Urade: "Recent advances in research on prostaglandin D,E,and F synthases" J.Lipid Mediators. (in press). (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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