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Roles of adenosine A2A receptors in sleep-wake regulation

Research Project

Project/Area Number 18603011
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 睡眠学
Research InstitutionOsaka Bioscience Institute

Principal Investigator

HUANG Zhi Li  Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Vice head (10321704)

Co-Investigator(Kenkyū-buntansha) URADE Yoshihiro  Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Head (10201360)
HAYAISHI Osamu  Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Researcher (40025507)
QU Wei Min  Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Researcher (20332231)
WADA Masashi  Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Researcher (80421379)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,050,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsAdenosine / A_1 receptor / A_<2A> receptor / Caffeine / Nucleus accumbens / Gene-manipulated mice / Sleep / Wakefulness / Adenosine / A1 receptor / A2A receptor / Knockout mice / Sleep / Wakefulness
Research Abstract

Adenosine is an inhibitory neuromodulator mediating the sleep-wake cycle. Several lines of evidence indicate that both adenosine Al receptor (R) and A2AR subtypes are involved in sleep induction. However, the magnitude of their contribution to sleep induction by adenosine remains controversial.
When given into the subarachnoid space under the basal forebrain, CGS21680, an A2AR agonist, induced strong non-rapid eye movement (non-REM) sleep in rodents. The increase of non-REM sleep could be mimicked by the activation of A_<2A>R in the nucleus accumbens (NAc) where the A_<2A>R is mostly distributed. Lesions of NAc changed sleep-wake profiles but the alteration was normalized to baseline level one week later, suggesting that the NAc may be an important target for sleep induction by A2AR. CGS21680 induced sleep through activation of sleep-active neurons in the ventrolateral preoptic area which sends inhibitory signals to suppress the histaminergic neurons in the tuberomammillary nucleus (TMN).
Although AIR has been proposed to be involved in the homeostatic regulation of sleep, no significant increase in sleep was observed after an AIR agonist was perfused into the lateral ventricle. Histaminergic TMN densely expresses adenosine deaminase, a metabolic enzyme of adenosine. Bilaterally injected into the rat TMN, coformycin, an adenosine deaminase inhibitor, or N6-cyclopentyladenosine, a selective AIR agonist, significantly and dose-dependently increased non-REM sleep, whereas REM sleep was not affected. Immunohistochemistry showed that the A_1R was moderately expressed in histaminergic neurons. In vivo microdialysis revealed that activation of A_1R or inhibition of adenosine deaminase in the TMN decreased histamine release in the brain. Therefore, activation of A_1R in the TMN inhibits histaminergic activity and induces non-REM sleep.
Our findings indicate that activation. of either A_<2A>R or A_1R induced sleep in a region-dependent manner.

Report

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

    (36 results)

All 2008 2007 2006

All Journal Article (25 results) (of which Peer Reviewed: 11 results) Presentation (11 results)

  • [Journal Article] Gene expression in the rat brain during prostaglandin D_2-and adenosinergically-induced sleep2008

    • Author(s)
      Terao A,Huang ZL,Wisorl JP,Mochizuki T,Gerashchenko D,Urade Y, and Kilduff TS
    • Journal Title

      J Neurochem 105

      Pages: 1480-1490

    • 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] Gene expression in the rat brain during prostaglandin D2- and adenosinergically-induced sleep2008

    • Author(s)
      Terao A, Huang ZL, Wisorl JP, Mochizuki T, Gerashchenko D, Urade Y, Kilduff TS.
    • Journal Title

      J Neurochem 105

      Pages: 1480-1490

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Gene expression in the rat brain during prostaglandin D2-and adenosinergically-induced sleep2008

    • Author(s)
      Terao A, Huang ZL, Wisorl JP, Mochizuki T, Gerashchenko D, Urade Y, Kilduff, TS
    • Journal Title

      J Neurochem 105

      Pages: 1480-1490

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prostaglandins and adenosine in the regulation of sleep and wakefulness2007

    • Author(s)
      Huang ZL,Urade Y and Hayaishi O.
    • Journal Title

      Curr Opin Pharmacol 7(1)

      Pages: 33-38

    • 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] Lipocalin-type PGD synthase is a major amyloid β-chaperone in human cerebrospinal fluid2007

    • Author(s)
      Kanekiyo T,Aritake S,Yamaguchi K,Huang ZL,Qu WM,Ozono K,Taniike M,Goto Y,Urade Y.
    • Journal Title

      Proc Natl Acad Sci USA 104(15)

      Pages: 6412-6417

    • 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] Deep brain stimulation of the posterior hypothalamus activates the histaminergic system to exert antiepileptic effect in rat pentylentetrazol model2007

    • Author(s)
      Namiko Nishida;Huang ZL,Nobuhiro Mikuni, et. al.
    • Journal Title

      Exp Neurol 205

      Pages: 132-144

    • 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] Adenosine A_<2A> receptors in ventral striatum, hypothalamus and nociceptive circuitry. Implications for drug addiction, sleep and pain2007

    • Author(s)
      Ferre S,Diamond I,Godlberg SR,Yao L,Hourani SMO,Huang ZL,Urade Y and Kitchen,I
    • Journal Title

      Prog Neurobiol 83

      Pages: 332-347

    • 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] Prostaglandins and adenosine in the regulation of sleep and wakefulness2007

    • Author(s)
      Huang ZL, Urade Y, Hayaishi O.
    • Journal Title

      Curr. Opin. Pharmacol. 7

      Pages: 33-38

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Lipocalin-type PGD Synthase is a major amyloid β-chaperone in human cerebrospinal fluid2007

    • Author(s)
      Kanekiyo T, Aritake S, Yamaguchi K, Huang ZL, Qu WM, Ozono K, Taniike M, Goto Y, Urade Y.
    • Journal Title

      Proc Natl Acad Sci USA 104(15)

      Pages: 6412-6417

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Deep brain stimulation of the posterior hypothalamus activates the histaminergic system to exert andtiepileptic effect in rat pentylentetrazol model2007

    • Author(s)
      Nishida N, Huang ZL, Mikuni N, Miura Y, Urade Y, Hashimoto N.
    • Journal Title

      Exp Neurol 205(1)

      Pages: 132-144

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry. Implications for drug addication, sleep and pain2007

    • Author(s)
      Ferre S, Diamond I, Godlberg SR, Yao L, Hourani SMO, Huang ZL, Urade Y, Kitchen I.
    • Journal Title

      Prog Neurobiol 83

      Pages: 332-347

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Prostaglandins and adenosine in the regulation of sleep and wakefulness2007

    • Author(s)
      Huang ZL, Uade Y, Hayaishi O.
    • Journal Title

      Curr Opin Pharmacol 7

      Pages: 33-38

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lipocalin-type PGD synthase is a major amyloid β-chaperone in human cerebrospinal fluid2007

    • Author(s)
      Kanekiyo T, Aritake S, Yamaguchi K, Huang ZL, Qu WM, Ozono K, Taniike M, Goto Y, Urade Y.
    • Journal Title

      Proc Natl Acad Sci USA 104

      Pages: 6412-6417

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prostaglandins and adenosine in the regulation of sleep and wakefulness2007

    • Author(s)
      Huang ZL, Urade Y, Hayaishi O.
    • Journal Title

      Curr Opin Pharmacol 7(1)

      Pages: 33-38

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Lipocalin-type PGD synthase is a major amyloid β-chaperone in human cerebrospinal fluid.2007

    • Author(s)
      Kanekiyo T, Ban T, Aritake K., Huang Z-L, Qu W-M, Okazaki I, Mohri I, Murayama S, Ozono K, Taniike M, Goto Y, Urade Y.
    • Journal Title

      Proc Natl Acad Sci USA 104(15)

      Pages: 6412-6417

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Deep brain stimulation of the posterior hypothalamus activates the histaminergic system to exert antiepileptic effect in rat pentylentetrazol model.2007

    • Author(s)
      Nishida N, Huang ZL, Mikuni N, et al.
    • Journal Title

      Exp Neurol (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Alterations of sleep-wake behavioral characteristics and lack of arousal response to H_3 receptor antagonist in histamine H_1 receptor knockout mice2006

    • Author(s)
      Huang ZL,Mochizuki T,Qu WM,Hong ZY,Watanabe T,Urade Y and Hayaishi O.
    • Journal Title

      Proc Natl Acad Sci USA 103(12)

      Pages: 4687-4692

    • 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] Lipocalin-type prostaglandin D synthase produces prostaglandin D_2 involved in regulation of physiological sleep2006

    • Author(s)
      Qu WM,Huang ZL,Xu XH,Aritake K,Eguchi O,Nambu F,Narumiya S,Urade Y and Hayaishi O.
    • Journal Title

      Proc Natl Acad Sci USA 103(47)

      Pages: 17949-17954

    • 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] Fasting-induced reduction in locomotor activity and reduced response of orexin neurons in camitine-deficient mice2006

    • Author(s)
      Yoshida G,Li MX,Horiuchi M,Nakagawa S,Sakata M,Kuchiiwa S,Kuchiiwa T,Jalil MA,Begum L,Lu YB,Iijima M,Hanada T,Nakazato M,Huang ZL, et. al.
    • Journal Title

      Neurosci Res 55(1)

      Pages: 78-86

    • 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] Altered sleep-wake characteristics and lack of arousal response to H3 receptor antagonist in histamine h1 receptor knockout mice2006

    • Author(s)
      Huang ZL, Mochizuki T, Qu WM, Hong ZY, Watanabe T, Urade Y, Hayaishi O.
    • Journal Title

      Proc Natl Aci USA 103(12)

      Pages: 4687-4692

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] and Hayaishi O. Lipocalin-type prostaglandin D synthase produces prostaglandin D2 involved in regulation of physiological sleep2006

    • Author(s)
      Qu WM, Huang ZL, Xu XH, Aritake K, Eguchi N, Nambu F, Narumiya S, Urade Y
    • Journal Title

      Proc Natl Acad Sci USA 103(47)

      Pages: 17949-17954

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Fasting-induced reduction in locomotro activity and reduced response of orexin neurons in carnitine-deficient mice2006

    • Author(s)
      Yoshida G, Li MX, Horiuchi M, Nakagawa S, Sakata M, Kuchiiwa S, Kuchiiwa T, Jalil MA, Begum L, Lu YB, Iijima M, Hanada T, Nakazato M, Huang ZL, Etal.
    • Journal Title

      Neurosci Res 55(1)

      Pages: 78-86

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Lipocalin-type prostaglandin D synthase produces prostaglandin D_2 involved in regulation of physiological sleep.2006

    • Author(s)
      Qu WM, Huang ZL, Xu XH, Aritake K, Eguchi N, Nambu F, Narumiya S, Urade Y, Hayaishi O.
    • Journal Title

      Proc Natl Acad Sci USA 103(47)

      Pages: 17949-17954

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Alterations of sleep-wake behavioral characteristics and lack of arousal response to H_3 receptor antagonist in histamine H_1 receptor knockout mice2006

    • Author(s)
      Huang ZL, Mochizuki T, Qu WM, Hong ZY, Watanabe T, Urade Y, Hayaishi O.
    • Journal Title

      Proc Natl Acad Sci USA 103(12)

      Pages: 4687-4692

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Fasting-induced reduction in locomotor activity and reduced response of orexin neurons in carnitine-deficient mice2006

    • Author(s)
      Yoshida G, Li MX, Horiuchi M, Nakagawa S, Sakata M, Kuchiiwa S, Kuchiiwa T, Jalil MA, Begum L, Lu YB, Iijima M, Hanada T, Nakazato M, Huang ZL, et al.
    • Journal Title

      Neurosci Res 55(1)

      Pages: 78-86

    • Related Report
      2006 Annual Research Report
  • [Presentation] Genetic dissection of the role of histaminergic systems in sleep-wake regulation2007

    • Author(s)
      Huang ZL.
    • Organizer
      Annual Meeting for the Hong Kong Society of Sleep Medicine
    • Place of Presentation
      Hong Kong,China
    • Year and Date
      2007-09-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Genetic dissection of the role of histaminergic systems in sleep-wake regulation2007

    • Author(s)
      Huang ZL.
    • Organizer
      Annual Meeting for the Hong Kong Society of Sleep Medicine
    • Place of Presentation
      Hong Kong, China
    • Year and Date
      2007-09-29
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Roles of the histaminergic systems in sleep-wake regulation2007

    • Author(s)
      Huang ZL.
    • Organizer
      The 3rd CINP Asia-Pacific Regional Meeting
    • Place of Presentation
      Bangkok,Thailand
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Prostaglandin D_2 system:recent progress in basic and clinical studies2007

    • Author(s)
      Huang ZL.
    • Organizer
      Worldsleep07: The 5th World Congress of the World, Federation of Sleep Research and Sleep Medicine Societies
    • Place of Presentation
      Cairns,Australia
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Sleep propensity is necessary for the sleep induction of histamine H_1 receptor antagonist2007

    • Author(s)
      Huang,ZL.,Qu,WM.,Matsumoto,N.,Wada,M.,Urade,Y.& Hayaishi, O.
    • Organizer
      The 32nd Annual Meeting of Japanese Sleep Research Society
    • Place of Presentation
      Tokyo,Japan
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Roles of the histaminergic systems in sleep-wake regulation2007

    • Author(s)
      Huang ZL.
    • Organizer
      The 3rd CINP Asia-Pacific Regional Meeting
    • Place of Presentation
      Bangkok, Thailand
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Prostaglandin D2 system : recent progress in basic and clinical studies2007

    • Author(s)
      Huang ZL.
    • Organizer
      Worldsleep07 : The 5th World Congress of the World, Federation of Sleep Research and Sleep Medicine Societies
    • Place of Presentation
      Cairns, Australia
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Sleep propensity is necessary for the sleep induction of histamine H1 receptor antagonist2007

    • Author(s)
      Huang, Z-L., Qu, W-M., Matsumoto, N., Wada, M., Urade, Y., Hayaishi, O.
    • Organizer
      The 32ad Annual Meeting of Japanes Sleep Research Society
    • Place of Presentation
      Tokyo, Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Roles of the histaminergic system in sleep-wake regulation by prostaglandin, adenosine and or2007

    • Author(s)
      Huang ZL
    • Organizer
      Worldsleep07, Conference for World Sleep Research Society
    • Place of Presentation
      Cairns, Australia
    • Related Report
      2007 Annual Research Report
  • [Presentation] Alterations of sleep-wake behavioral 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.
    • Organizer
      The 20th International Congress of Biochemistry and Molecular Biology
    • Place of Presentation
      Kyoto,Japan
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Alterations of sleep-wake behavioral characteristics and lack of arousal response to H3 receptor antagonist in histamine H1 receptor knockout mice2006

    • Author(s)
      Huang, Z.L., Mochizuki, T., Qu, W. M., Hong, Z. Y., Watanabe, T., Urade, Y., Hayaishi, O.
    • Organizer
      The 20th International Congress of Biochemistry and Molecular Biology
    • Place of Presentation
      Kyoto, Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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

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