2005 Fiscal Year Final Research Report Summary
Molecular mechanism of wakefulness regulation
| Project/Area Number |
16300123
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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 |
HAYAISHI Osamu Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Researcher, 分子行動生物学部門, 研究員 (40025507)
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| Co-Investigator(Kenkyū-buntansha) |
URADE Yoshihiro Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Head, 分子行動生物学部門, 研究部長 (10201360)
HUANG Zhi-Li Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Vice Head, 分子行動生物学部門, 研究副部長 (10321704)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Wakefulness / Brief awakening / Gene knockout mice / Histamine / TMN / GABA / A_<2A> receptor / Caffeine |
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| Research Abstract |
Under baseline conditions, gene knockout (KO) mice for histamine H_1 receptors (H_1R) showed sleep-wake cycles essentially identical to those of wild-type (WT) mice but with fewer incidents of brief awakening (<16-sec epoch) during non-rapid eye movement (NREM) sleep and a shorter latency for initiating NREM sleep after an i.p. injection of saline. The H_1R antagonist, pyrilamine, mimicked these effects in WT mice. A histamine H_3 receptor antagonist, ciproxifan, increased wakefulness in WT mice after an i.p. injection in a dose-dependent manner but not at all in H_1R KO mice, although the histamine release from the frontal cortex was increased in both genotypes of mice. These results indicate that H_1R is involved in the regulation of state transitions from NREM sleep to wakefulness and that the arousal effect of the H_3 antagonist completely depends on the activation of histaminergic system through H_1R.
Administration of an adenosine A_<2A> receptor (A_<2A>R) agonist, CGS21680, to th
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e rat basal forebrain inhibited both wakefulness and the histamine release in the frontal cortex. Microdialysis studies with anesthetized rats revealed that the A_<2A>R-agonist administration inhibited the histamine release in the cortex and increased the GABA release in the histaminergic tuberomammillary nucleus (TMN) but not in the cortex. The A_<2A>R-agonist-induced inhibition of the histamine release was reversed by the administration of GABA antagonist, picrotoxin, into the TMN, indicating that the GABAergic inhibition of TMN was involved in the inhibition of wakefulness by A_<2A>R agonist. Caffeine is the most popular substance to induce wakefulness but the receptor subtype involved in the caffeine-induced wakefulness remained unclear. When we administrated caffeine in WT, adenosine A_1 receptor (A_1R)-KO, and A_<2A>R-KO mice, caffeine induced wakefulness in WT and A_1R-KO mice but not at all in A_<2A>R-KO mice, indicating that the arousal effect of caffeine completely depends on A_<2A>R, but not A_1R. Less
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[Journal Article] Altered sleep-wake characteristics and lack of arousal response to H_3 receptor antagonist in histamine H_1 receptor knockout mice2006
Author(s)
Huang, Z.-L., Mochizuki, T., Qu, W.-M., Hong, Z.-Y., Watanabe, T., Urade, Y., Hayaishi, O.
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Journal Title
Proc.Natl.Acad.Sci.USA 103
Pages: 4687-4692
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Adenosine A_<2A>, but not A_1, receptors mediate the arousal effect of caffeine2005
Author(s)
Huang, Z.-L., Qu, W-M., Eguchi, N., Chen, J.-F., Schwarzschild, M.A., Fredholm, B.B., Urade, Y., Hayaishi, O
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Journal Title
Nat.Neurosci. 8
Pages: 858-859
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The endogenous somnogen adenosine excites a subset of sleep-promoting neurons via A_<2A> receptors in the ventrolateral preoptic nucleus.2005
Author(s)
Gallopin, T., Luppi, P.-H., Cauli, B., Urade, Y., Rossier, J., Hayaishi, O., Lambolez, B., Fort, P
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Journal Title
Neuroscience 134
Pages: 1377-1390
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Preface.2005
Author(s)
Hayaishi, O., Coon, M.J., Estabrook, R.W., Que, L., Yamamoto, S
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Journal Title
Biochem.Biophys.Res.Commun. 338
Pages: 1
Description
「研究成果報告書概要(欧文)」より
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