2014 Fiscal Year Annual Research Report
| Project/Area Number |
24300129
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| Research Institution | University of Tsukuba |
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Principal Investigator |
ラザルス ミハエル 筑波大学, 国際統合睡眠医科学研究機構, 准教授 (80469650)
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| Co-Investigator(Kenkyū-buntansha) |
大石 陽 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (70554004)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | Sleep / Caffeine / Adeno-associated virus / Optogenetics / Pharmacogenetics / Adenosine / Nucleus accumbens |
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| Outline of Annual Research Achievements |
The sleeping habits of humans are unique in the sense that we often defy sleep and stay awake for occupational and recreational reasons or other life-style choices. The motivation to defy sleep and stay awake for a wide range of life-style choices is often accompanied by the use of psychoactive substances, most prominently caffeine, but also prescription drugs such as Modafinil.
We have demonstrated that caffeine induces wakefulness by blocking the action of adenosine on A2A receptors (A2AR) in the nucleus accumbens (NAc; Lazarus M, et al., J. Neurosci. 2011, p. 10067). Adenosine promotes sleep, however the extent to which these A2AR-positive NAc neurons contribute to sleep regulation was previously unknown. Pharmacological activation of A2ARs by the agonist CGS21680 increased non rapid eye movement (NREM) sleep in wild type, but not NAc-specific A2AR KO mice. Optogenetic (channelrhodopsin, ChR2) activation of NAc A2AR neurons induces robust NREM sleep.
Our observations provide the first direct evidence that adenosine and A2AR neurons in the NAc are not only involved in promoting behavioral inactivity (inhibition of movement) but also play a major role in regulating sleep. These findings further suggest the intriguing possibility that the NAc might be a key site through which sleep and wakefulness are regulated by behavioral processes and, by extension, that motivational state may be an important fundamental regulator of sleep and wakefulness (Lazarus M, et al., Trends Neurosci. 2012, p. 723; Lazarus M, et al., Curr. Opin. Neurobiol. 2013, p. 780).
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| Research Progress Status |
26年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
26年度が最終年度であるため、記入しない。
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| Causes of Carryover |
26年度が最終年度であるため、記入しない。
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| Expenditure Plan for Carryover Budget |
26年度が最終年度であるため、記入しない。
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[Journal Article] EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-β1 signaling2015
Author(s)
Lu A, Zuo C, He Y, Chen G, Piao L, Zhang J, Xiao B, Shen Y, Tang J, Kong D, Alberti S, Chen D, Zuo S, Zhang Q, Yan S, Yuan F, Zhou B, Duan SZ, Yu Y, Lazarus M, Su Y, Breyer R, Funk C, Yu Y
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Journal Title
Journal of Clinical Investigation
Volume: 125
Pages: 1228-1242
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Introduction to Sleep2014
Author(s)
Lazarus, Michael
Organizer
Tokyo Translational Therapeutics Meeting
Place of Presentation
Ito Hall, The University of Tokyo (Tokyo, Bunkyo-ku)
Year and Date
2014-09-24
Invited
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