Roles of adenosine A2A receptors in sleep-wake regulation
| Project/Area Number |
18603011
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
睡眠学
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| Research Institution | Osaka Bioscience Institute |
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Principal Investigator |
HUANG Zhi Li Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Vice head (10321704)
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| 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)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| 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)
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| Keywords | Adenosine / A_1 receptor / A_<2A> receptor / Caffeine / Nucleus accumbens / Gene-manipulated mice / Sleep / Wakefulness / Adenosine / A1 receptor / A2A receptor / Knockout mice / Sleep / Wakefulness |
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| 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.
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Report
(3 results)
Research Products
(36 results)
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[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.
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Journal Title
Proc Natl Acad Sci USA 104(15)
Pages: 6412-6417
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[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.
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Journal Title
Neurosci Res 55(1)
Pages: 78-86
Description
「研究成果報告書概要(和文)」より
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Peer Reviewed
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[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.
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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
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[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.
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Journal Title
Neurosci Res 55(1)
Pages: 78-86
Related Report
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[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
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[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
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[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
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[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
