Mechanisms and roles of orexins in the regulation of sleep/wakefuless states

2008 Fiscal Year Self-evaluation Report

• Project/Area Number: 18209008
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: University of Tsukuba
• Principal Investigator: MATSUZAKI Ichiyo University of Tsukuba, 大学院・人間総合科学研究科, 教授 (10229453)
• Project Period (FY): 2006 – 2009
• Keywords: 生理活性物質

Research Abstract

睡眠・覚醒の制御機構におけるオレキシンの生理的役割を解明するため以下の研究を遂行する。
(1)オレキシンのもつ睡眠・覚醒の制御、摂食行動の制御にかかわる機構を解明する。とくに二つの受容体サブタイプが睡眠・覚醒の制御、およびエネルギー恒常性の制御に果たす役割と神経機構を明らかにする。
(2)オレキシン産生神経(オレキシン神経)の活性に影響をあたえる因子を網羅的に調べ、その作用機序も明らかにすることにより、オレキシン神経が生体内でどのように制御されているかを解明する一助にする。
(3)オレキシン産生神経の活動様式をin vivoの系で明らかにし、睡眠・覚醒や、行動との相関を明らかにする。
(4)In vitroの系でオレキシン神経の制御機構における情報伝達系を明らかにする。
(5)オレキシン神経の制御機構の生理的重要性をin vivoで明らかにする。

Research Products

• [Journal Article] Thyrotropin-Releasing Hormone Increases Behavioral Arousal through Modulation of Hypocretin/Orexin Neurons (2009)
  • Author(s): Hara, J. Gerashchenko, D, Wisor, J.P., Sakurai, T., Xie, X., and Kilduff, T.S.
  • Journal Title: J. Neurosci 29(12) Pages: 3705-3714
• [Journal Article] Selective loss of GABA_B receptors in orexin/hypocretin-producing neurons results in disrupted sleep/wakefulness architecture (2009)
  • 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.
  • Journal Title: Proc. Natl.Acad., Sci., USA. 106(11) Pages: 4459-64
• [Journal Article] Enhanced Orexin Signaling Prevents Diet-Induced Obesity and Improves Leptin Sensitivity (2009)
  • Author(s): Funato, H., Tsai, A., Willie, J.T., Kisanuki, Y., Williams, S.C., Sakurai, T. & Yanagisawa, M.
  • Journal Title: Cell Metab 9(1) Pages: 64-76
• [Journal Article] Neural Circuit of Orexin (Hypocretin) : Mainaining Sleep and Wakefulness (2007)
  • Author(s): Sakurai T.
  • Journal Title: Nat. Rev. Neurosci 8 Pages: 171-181
• [Presentation] Acute and Chronic Regulation of Sleep-Wakefulness States by Orexin/Hypocretin Neurons (2008)
  • Author(s): Sakurai, T
  • Organizer: SfN meeting, Washington D.C
  • Place of Presentation: USA
  • Year and Date: 20081112-16
• [Presentation] The Neural Circuit of Orexin : Mechanisms for Maintaining Sleep and Wakefulness (2008)
  • Author(s): Sakurai, T
  • Organizer: 2nd WFSBP Asia-Pacific Congress and 30th Annual Meeting of JSBP
  • Place of Presentation: Toyama, Japan
  • Year and Date: 20080911-20080913
• [Presentation] Roles of orexin/hypocretin system in the regulation of sleep-waking cycle (2008)
  • Author(s): Sakurai, T
  • Organizer: Acta Physiologica International Symposium
  • Place of Presentation: Oulu, Finland
  • Year and Date: 20080813-20080814
• [Presentation] Acute and Chronic Regulation of Sleep-Wakefulness States by Orexin/Hypocretin Symposium S02 at Sleep2008 (22^<nd> APSS annual meeting) (2008)
  • Author(s): Sakurai, T
  • Organizer: Baltimore, MD
  • Place of Presentation: USA
  • Year and Date: 20080607-12
• [Book] Results Probl Cell Differ 41 Orphan G protein-coupled receptors and novel neuropeptides.Ed. Civerlli, O and Zhou QY. (2008)
  • Author(s): Matsuki T, Sakurai T. Orexins, Orexin Receptors
  • Total Pages: 46:27-55
  • Publisher: From Molecules to Integrative Physiology
• [Book] Results Probl Cell Differ. Results Probl Cell Differ 41 Orphan G protein-coupled receptors and novel neuropeptides. Ed. Civerlli, O and Zhou QY (2008)
  • Author(s): Hondo M, Ishii M, Sakurai T.
  • Total Pages: 46 : 239-56
  • Publisher: The NPB/NPW Neuropeptide System and Its Role in Regulating Energy Homeostasis, Pain, and Emotion