2007 Fiscal Year Final Research Report Summary
Crosstalk of signal transduction in sleep-wake regulation
| Project/Area Number |
18300129
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Osaka Bioscience Institute |
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Principal Investigator |
HAYASHI Osamu Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Researcher (40025507)
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| Co-Investigator(Kenkyū-buntansha) |
URADE Yoshihiro Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Head (10201360)
HUANG Zhi Li Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Vice head (10321704)
QU Wei Min Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Researcher (20332231)
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| Project Period (FY) |
2006 – 2007
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| Keywords | leep-wake cycle / sleep substances / neural network / humoral regulation |
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| Research Abstract |
Administration of SeC14, a selective inhibitor of prostaglandin (PG) D synthase (PGDS), inhibited sleep dose-dependently in wild-type or hematopoietic PGDS knockout (KO) mice but not at all in lipocalin-type PGDS KO, hematopoietic and lipocalin-type PGDS double KO or PGD receptor (DP1R) KO mice. Furthermore, the DP1R antagonist reduced sleep of rats during infusion into the subarachnoid space under the rostral basal forebrain. These results clearly show that lipocalin-type PGDS/PGD2/DP1R system plays pivotal roles in the regulation of physiological sleep.
PGD_2 promotes sleep by activation of a sleep-center in the ventrolateral pre-optic area, and suppression of the wake-center in the histaminergic tuberomammillary nucleus (TMN). When we examined sleep-wake cycles of histamine H_1 receptors (H_1R) KO mice, H_1R KO mice showed sleep-wake cycles with fewer incidents of brief awakening, indicating that H_1R was involved in the regulation of behavioral state transitions from non-rapid eye movement (NREM) sleep to wakefulness.
Histaminergic TMN contains adenosine deaminase. Inhibition of adenosine deaminase or activation of adenosine A_1 receptor in the TMN increased NREM sleep and suppressed the histamine release in the brain. These results that indicate adenosine suppresses histaminergic activity and induces NREM sleep via A_1 receptors.
Histaminergic system had been implicated in the arousal effect of modafinil. However, we found that modafinil induced wakefulness in both H_1R KO and wild-type mice, indicating that histaminergic system was not essential for the modafinil-induced wakefulness. However, dopamine D_2 receptor KO mice exhibited attenuated modafinil-induced wakefulness. Moreover, pretreatment of D_2 receptor KO mice with Di receptor antagonist completely abolished arousal effects of modafinil. These findings indicate that the dopaminergic D_1 and D_2 receptor are essential for the wakefulness induced by modafinil.
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[Journal Article] Odyssey of a Biochermist.2007
Author(s)
Hayaishi, O.
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Journal Title
Comprehensive Biochemistry : Stories of Success-Personal Recollections. X. Ed. Semenza, G., Elsevier B. V. Vol.45
Pages: 1-36
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 眠りの秘密2007
Author(s)
早石 修
Organizer
大阪医科大学創立80周年記念特別市民講演会
Place of Presentation
高槻市立文化ホール「現代劇場」(大阪)
Year and Date
2007-12-22
Description
「研究成果報告書概要(和文)」より
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[Presentation] 眠りの謎2007
Author(s)
早石 修
Organizer
日本学士院第2部談話会
Place of Presentation
日本学士院(東京)
Year and Date
2007-03-12
Description
「研究成果報告書概要(和文)」より
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[Presentation] 眠りの秘密2006
Author(s)
早石 修
Organizer
日本睡眠学会第31回定期学術集会 教育講演
Place of Presentation
大津プリンスホテル(滋賀)
Year and Date
2006-06-29
Description
「研究成果報告書概要(和文)」より
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[Presentation] The birth of oxygenases2006
Author(s)
Osamu Hayaishi
Organizer
Commemorative Symposium "Structures and functions of oxygenases: In commemoration of the 50th anniversary of the discovery of oxygenases" 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
Place of Presentation
Kyoto International Conference Hall,Kyoto,Japan
Year and Date
2006-06-19
Description
「研究成果報告書概要(和文)」より
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[Presentation] The birth of oxygenases2006
Author(s)
Osamu Hayaishi
Organizer
Commemorative Symposium Structures and functions of oxygenases : In commemoration of the 50th anniversary of the discovery of oxygenases 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
Place of Presentation
Kyoto International Conference Hall, Kyoto, Japan
Year and Date
2006-06-19
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The birth of oxygenases2006
Author(s)
Osamu Hayaishi
Organizer
The 14th Takeda Science Foundation Symposium on Bioscience "The 50th anniversary of oxygenases-advances and reflections-"
Place of Presentation
Kyoto Hotel Okura,Kyoto,Japan
Year and Date
2006-04-10
Description
「研究成果報告書概要(和文)」より
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[Presentation] The birth of oxygenases2006
Author(s)
Osamu Hayaishi
Organizer
The 14th Takeda Science Foundation Symposium on Bioscience The 50th anniversary of oxygenases -advances and reflections-
Place of Presentation
Kyoto Hotel Okura, Kyoto, Japan
Year and Date
2006-04-10
Description
「研究成果報告書概要(欧文)」より
