2009 Fiscal Year Final Research Report
Roles of orexins in regulation of sleep/wake states
| Project/Area Number |
18209008
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
MATSUZAKI Ichiyo University of Tsukuba, 大学院・人間総合科学研究科, 教授 (10229453)
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| Co-Investigator(Kenkyū-buntansha) |
SAKURAI Takeshi 金沢大学, 大学院・医学系研究科, 教授 (60251055)
IRUKAYAMA Yoko 筑波大学, 大学院・人間総合科学研究科, 講師 (90312834)
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| Project Period (FY) |
2006 – 2009
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| Keywords | オレキシン / 睡眠 / 覚醒 / パソプレッシン / TRH / アセチルコリン / GABA |
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| Research Abstract |
We have identified several factors that influence activity of orexin-producing neurons, including vasopressin, neurotensin, and thyrotropin-releasing hormone (TRH). We also revealed that orexin-producing neurons express an orphan receptor, BRS-3, which might be also involved in the regulation of orexin neurons. The activation of orexin neurons by vasopressin has an important role in the regulation of spontaneous locomotor activity in mice. This system appears to play a role in water deprivation-induced hyperlocomotor activity, a response to dehydration that increases the chance of locating water in nature. We also found that thyrotropin-releasing hormone modulates behavioral arousal and sympathetic outflow, in part, through the orexin system. We also analyze the in vivo and in vitro phenotype of mice lacking the GABA_<B1> gene specifically in orexin neurons, and demonstrate that GABA_B receptors on orexin neurons are essential in stabilizing and consolidating sleep/wake states.
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[Journal Article] Hypothalamic orexin stimulates feeding-associated glucose utilization in skeletal muscle via sympathetic nervous system2009
Author(s)
Shiuchi, T., Haque, M.S., Okamoto, S., Inoue, T., Kageyama, H., Lee, S, Toda, C., Suzuki, A., Bachman, E.S., Kim, Y-B., Sakurai, T., Yanagisawa, M., Shioda, S., Imoto, K., Minokoshi, Y.
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Journal Title
Cell Metab 10
Pages: 466-480
Peer Reviewed
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[Journal Article] Thyrotropin-Releasing Hormone Increases Behavioral Arousal through Modulation of Hypocretin/Orexin Neurons2009
Author(s)
Hara, J. Gerashchenko, D, Wisor, J. P., Sakurai, T., Xie, X., Kilduff, T. S.
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Journal Title
J.Neurosci. 29
Pages: 3705-3714
Peer Reviewed
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[Journal Article] Aromatic D-amino acids act as chemoattractant factors for human leukocytes through a G protein-coupled receptor GPR109B2009
Author(s)
Irukayama-Tomobe, Y, Tanaka, H., Yokomizo, T., Hashidate-Yoshida, T., Yanagisawa, M., Sakurai, T.
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Journal Title
Proc.Natl.Acad.,Sci.,USA. 106
Pages: 3930-3934
Peer Reviewed
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[Journal Article] Selective loss of GABA_B receptors in orexin/hypocretin-producing neurons results in disrupted sleep/wakefulness architecture2009
Author(s)
Matsuki, T., Nomiyama, M, Takahira, H., Hirashima, N., Kilduff, T. S., Kunita, S., Takahashi, S., Yagami, K., Bettler, B., Yanagisawa, M., Sakurai, T.
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Journal Title
Proc.Natl.Acad.,Sci.,USA 106
Pages: 4459-64
Peer Reviewed
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[Journal Article] IGFBP3 colocalizes with and regulates hypocretin (orexin)2009
Author(s)
Honda, M., Eriksson, K. S., Zhang, S., Tanaka, S., Lin, L., Salehi, A., Hesla, P. E., Maehlen, J., Gaus, S. E., Yanagisawa, M., Sakurai, T., Taheri, S., Tsuchiya, K., Honda, Y., Mignot, E.
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Journal Title
Peer Reviewed
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[Journal Article] Enhanced Orexin Signaling Prevents Diet-Induced Obesity and Improves Leptin Sensitivity2009
Author(s)
Funato, H., Tsai, A., Willie, J. T., Kisanuki, Y., Williams, S. C., Sakurai, T., Yanagisawa, M.
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Journal Title
Cell Metab 9
Pages: 64-76
Peer Reviewed
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[Journal Article] Identification of a population of sleep-active cerebral cortex neurons2008
Author(s)
Gerashchenko, D., Wisor, J. P., Burns, D., Reh, R. K., Shiromani, P. J., Sakurai, T., de la Iglesia, H. O., Kilduff, T. S.
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Journal Title
Proc.Natl.Acad.,Sci.,USA. 105
Pages: 10227-10232
Peer Reviewed
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[Journal Article] Hypocretin/orexin & nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia2008
Author(s)
Xie, X, Wisor, JP, Hara, J, Crowder, TL, Lewinter, R, Khroyan, T. V., Yamanaka, A., Diano, S., Horvath, T. L., Sakurai, T., Toll, L., Kilduff, T. S.
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Journal Title
J Clin Invest 118
Pages: 2471-81
Peer Reviewed
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[Journal Article] Vasopressin increases locomotion through a V1a receptor in orexin/hypocretin neurons : implications for water homeostasis2008
Author(s)
Tsunematsu, T, Fu, L. Y., Yamanaka, A., Ichiki, K., Tanoue, A., Sakurai, T, van den Pol A. N.
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Journal Title
J Neurosci 28
Pages: 228-238
Peer Reviewed
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[Journal Article] A neuropeptide ligand of the G protein-coupled receptor GPR103 regulates feeding, behavioral arousal, and blood pressure in mice2006
Author(s)
Takayasu S, Sakurai T, Iwasaki S, Teranishi H, Yamanaka A, Williams SC, Iguchi H, Kawasawa YI, Ikeda Y, Sakakibara I, Ohno K, Ioka RX, Murakami S, Dohmae N, Xie J, Suda T, Motoike T, Ohuchi T, Yanagisawa M, Sakai J.
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Journal Title
Proc Natl Acad Sci USA. 103
Pages: 7438-43
Peer Reviewed
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[Journal Article] Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviors induced by morphine2006
Author(s)
Narita M, Nagumo Y, Hashimoto S, Narita M, Khotib J, Miyatake M, Sakurai T, Yanagisawa M, Nakamachi T, Shioda S, Suzuki T.
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Journal Title
J Neurosci 26
Pages: 398-405
Peer Reviewed
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[Journal Article] Uterine sensitization-associated gene-1 (USAG-1), a novel BMP antagonist expressed in the kidney, accelerates tubular injury2006
Author(s)
Yanagita M, Okuda T, Endo S, Tanaka M, Takahashi K, Sugiyama F, Kunita S, Takahashi S, Fukatsu A, Yanagisawa M, Kita T, Sakurai T.
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Journal Title
J Clin.Invest. 116
Pages: 70-79
Peer Reviewed
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