Studies of Novel Neuropeptides involved in Regulation of Emotional Reaction and Amygdala Function

• Project/Area Number: 20020010
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kanazawa University
• Principal Investigator: SAKURAI Takeshi Kanazawa University, 医学系, 教授 (60251055)
• Co-Investigator(Kenkyū-buntansha): YAMAMOTO Miyuki 筑波大学, 人間総合科学研究科, 准教授 (80143147)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥23,600,000 (Direct Cost: ¥23,600,000); Fiscal Year 2009: ¥9,100,000 (Direct Cost: ¥9,100,000); Fiscal Year 2008: ¥14,500,000 (Direct Cost: ¥14,500,000)
• Keywords: 扁桃体 / 情動 / 自律神経 / 神経ペプチド / NPBWR1 / fMRI / SNP / QRFP / ストレス / G蛋白質共役受容体 / GPR7 / 神経ペプチドB / 神経ペプチドW

Research Abstract

We investigated the physiological roles of three neuropeputide systems in the regulation of emotional reaction and amygdala function. We report here that neuropeptide B/W receptor1 (NPBWR1) plays a critical role in amygdala function mediating stress response and social behavior in both mice and humans. We have established QRFP-deficient mice for studying the role of this peptide in near future.

Research Products

• [Journal Article] Activation of Bombesin Receptor Subtype-3 influences Activity of Orexin Neurons by both direct and indirect Pathways. (2010)
  • Author(s): Furutani, N., et al.
  • Journal Title: J.Mol.Neurosci. (in press)
  • Peer Reviewed
• [Journal Article] Histamine-1 receptor is not required as a downstream effector of orexin-2 receptor in maintenance of basal sleep/wake states. (2010)
  • Author(s): Hondo, M.
  • Journal Title: Acta Physiol(Oxf) (in press)
  • Peer Reviewed
• [Journal Article] Circadian characteristics of mice depleted with GPR7. (2009)
  • Author(s): Uchio, N, Doi, M, Matsuo, M, Yamazaki, F, Mizoro, Y, Hondo, M, Sakurai, T, Okamura, H.
  • Journal Title: Biomed Res. 30 Pages: 357-364
  • Peer Reviewed
• [Journal Article] Hypothalamic orexin stimulates feeding-associated glucose utilization in skeletal muscle via sympathetic nervous system. (2009)
  • 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.
  • Journal Title: Cell Metab. 10 Pages: 466-480
  • Peer Reviewed
• [Journal Article] Orexin neurons in the hypothalamus mediate cardiorespiratory responses induced by disinhibition of the amygdala and bed nucleus of the stria terminalis. (2009)
  • Author(s): Zhang, W., Zhang, N., Sakurai, T., Kuwaki, T.
  • Journal Title: Brain Res 1262 Pages: 25-37
  • Peer Reviewed
• [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., Kilduff, T.S.
  • Journal Title: J. Neurosci. 29 Pages: 3705-3714
  • Peer Reviewed
• [Journal Article] Aromatic D-amino acids act as chemoattractant factors for human leukocytes through a G protein-coupled receptor GPR109B. (2009)
  • Author(s): Irukayama-Tomobe, Y, Tanaka, H., Yokomizo, T., Hashidate-Yoshida, T., Yanagisawa, M., Sakurai, T.
  • Journal Title: Proc. Natl. Acad., Sci., USA. 106 Pages: 3930-3934
  • Peer Reviewed
• [Journal Article] Selective loss of GABAB 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 Pages: 4459-64
  • Peer Reviewed
• [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.
  • Journal Title: PLoS ONE. 4
  • Peer Reviewed
• [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 Pages: 64-76
  • Peer Reviewed
• [Journal Article] Hypothalamic orexin stimulates feeding-associated glucose utilization in skeletal muscle via sympathetic nervous system. (2009)
  • Author(s): Shiuchi, T., et al.
  • Journal Title: Cell Metab 10 Pages: 466-480
  • Peer Reviewed
• [Journal Article] Thyrotropin-Releasing Hormone Increases Behavioral Arousal through Modulation of Hvnocretin/Orexin Neurons (2009)
  • Author(s): Hara, J., et.al.
  • Journal Title: J. Neurosci 29 Pages: 3705-3714
  • Peer Reviewed
• [Journal Article] Aromatic D-amino acids act, as chemoattractant factors for human leukocytes through a G protein-coupled receptor GPR109B (2009)
  • Author(s): Irukayama, Y., et.al.
  • Journal Title: Proc. Natl. Acad., Sci., USA 106 Pages: 3930-3934
  • Peer Reviewed
• [Journal Article] Selective loss of GABA_B receptors in orexin/hypocretin-producing neurons results in disrupted sleep/wakefulness architecture (2009)
  • Author(s): Matsuki, T., et.al.
  • Journal Title: Proc. Natl. Acad., Sci., USA 106 Pages: 4459-4464
  • Peer Reviewed
• [Journal Article] IGFBP3 colocalizes with and regulates hypocretin (orexin) (2009)
  • Author(s): Honda M., et.al.
  • Journal Title: PLoS ONE 4
  • Peer Reviewed
• [Journal Article] Enhanced Orexin Signaling Prevents Diet-Induced Obesity and Improves Leptin Sensitivity (2009)
  • Author(s): Funato, H., et.al.
  • Journal Title: Cell Metab 9 Pages: 64-76
  • Peer Reviewed
• [Journal Article] The NPB/NPW neuropeptide system and its role in regulating energy homeostasis, pain, and emotion. (2008)
  • Author(s): Hondo, M., Ishii, M., Sakurai, T.
  • Journal Title: Results Probl Cell Differ 46 Pages: 239-256
  • Peer Reviewed
• [Journal Article] Effect of neuropeptide B on feeding behavior is influenced by endogenous corticotropin-releasing factor activities. (2008)
  • Author(s): Aikawa, S., Ishii, M., Yanagisawa, M., Sakakibara, Y., Sakurai, T.
  • Journal Title: Regul Pept. 151 Pages: 147-152
  • Peer Reviewed
• [Journal Article] Identification of a population of sleep-active cerebral cortex neurons. (2008)
  • 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.
  • Journal Title: Proc. Natl. Acad., Sci., USA. 105 Pages: 10227-10232
  • Peer Reviewed
• [Journal Article] Hypocretin/orexin & nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia. (2008)
  • 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.
  • Journal Title: J Clin Invest. 118 Pages: 2471-81
  • Peer Reviewed
• [Journal Article] Vasopressin increases locomotion through a V1a receptor in orexin/hypocretin neurons: implications for water homeostasis. (2008)
  • Author(s): Tsunematsu, T, Fu, L.Y., Yamanaka, A., Ichiki, K., Tanoue, A., Sakurai, T, van den Pol A.N.
  • Journal Title: J Neurosci. 28 Pages: 228-238
  • Peer Reviewed
• [Journal Article] Cholinergic Regulation of Orexin/Hypocretin Neurons through M3 Muscarinic Receptor in mice (2008)
  • Author(s): Ohno, K., Hondo, M., Sakurai, T.
  • Journal Title: J. Pharmacol. Sci. 106 Pages: 485-91
  • Peer Reviewed
• [Journal Article] New developments in sleep research : molecular genetics, gene expression, and systems neurobiology (2008)
  • Author(s): Kilduff TS., et.al.
  • Journal Title: J Neurosci 28 Pages: 11814-11818
  • Peer Reviewed
• [Journal Article] Orexin (hypocretin) gene transfer diminishes narcoleptic sleep behavior in mice (2008)
  • Author(s): Liu M., et.al.
  • Journal Title: Eur J Neurosci 31 Pages: 1119-26
  • Peer Reviewed
• [Journal Article] Effect of neuropeptide B on feeding behavior is influenced by endogenous corticotropin-releasing factor activities (2008)
  • Author(s): Aikawa S., et.al.
  • Journal Title: Regul Pept 151 Pages: 147-152
  • Peer Reviewed
• [Journal Article] Identification of a population of sleep-active cerebral cortex neurons (2008)
  • Author(s): Gerashchenko, D., et.al.
  • Journal Title: Proc. Natl. Acad., Sci., USA 105 Pages: 10227-10232
  • Peer Reviewed
• [Journal Article] Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analaesia in a mouse model of stress-induced analgesia (2008)
  • Author(s): Xie X,., et.al.
  • Journal Title: J Clin Invest 118 Pages: 2471-2481
  • Peer Reviewed
• [Journal Article] Entrainment of temperature and activity rhythms to restricted feeding in orexin knock out mice (2008)
  • Author(s): Kaur S., et.al.
  • Journal Title: Brain Res. 1205 Pages: 47-54
  • Peer Reviewed
• [Journal Article] Enhanced BMP signaling results in supernumerary tooth formation in USAG-1 deficient mouse (2008)
  • Author(s): Murashima-Suginami, A., et.al.
  • Journal Title: Biochem Biophys Res Commun 369 Pages: 1012-1016
  • Peer Reviewed
• [Journal Article] Age-related insulin resistance in hypothalamus and peripheral tissues of orexin knockout mice (2008)
  • Author(s): Tsuneki H., et.al.
  • Journal Title: Diabetologia 51 Pages: 657-667
  • Peer Reviewed
• [Presentation] 扁桃体におけるNPBWR1の役割 (2010)
  • Author(s): 桜井武
  • Organizer: 第7回GPCR研究会
  • Place of Presentation: 東京
• [Presentation] Genetic variation of NPBWR1 alters amygdala function. (2010)
  • Author(s): Sakurai, T.
  • Organizer: Neuroendocrine Function of GPCRs (GPCR2010). Official Satelite Symposium of the 14th International Congress on Endocrinology, Kyoto
  • Place of Presentation: Kyoto
• [Presentation] Orexin as a waking substance. (2010)
  • Author(s): Sakurai, T.
  • Organizer: Turkish-Japanese Sleep Forum 2010
  • Place of Presentation: Izmir, Turky
• [Presentation] Roles of orexins in regulation of energy homeostasis. (2010)
  • Author(s): Sakurai, T.
  • Organizer: Symposium of the 14th International Congress on Endocrinology
  • Place of Presentation: Kyoto
• [Presentation] Genetic variation of NPBWR1 alters amygdala function. Neuroendocrine Function of GPCRs(GPCR2010). (2010)
  • Author(s): Sakurai, T.
  • Organizer: Official Satelite Symposium of the 14^<th> International Congress on Endocrinology
  • Place of Presentation: 京都国際会議場(京都)
• [Presentation] 新規神経ペプチドとその生理機能の探求 (2009)
  • Author(s): 桜井武
  • Organizer: 第1回Advans研究会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-12-26
• [Presentation] 新規神経ペプチドと睡眠・覚醒・情動 (2009)
  • Author(s): 桜井武
  • Organizer: 第56回中部日本生理学会
  • Place of Presentation: 金沢
  • Year and Date: 2009-12-04
• [Presentation] 新規神経ペプチドと精神機能 (2009)
  • Author(s): 桜井武
  • Organizer: 「社会性認識」学際脳科学シンポジウム
  • Place of Presentation: 金沢
  • Year and Date: 2009-11-06
• [Presentation] A decade of research on orexin. (2009)
  • Author(s): Sakurai, T
  • Organizer: The 36th Congress of the International Union of Physiological Sciences
  • Place of Presentation: Kyoto
  • Year and Date: 2009-07-29
• [Presentation] オレキシン産生神経による睡眠・覚醒の安定化機構 (2009)
  • Author(s): 桜井武
  • Organizer: 日本実験動物学会総会シンポジウム3
  • Place of Presentation: 大宮
  • Year and Date: 2009-05-15
• [Presentation] オレキシンによる睡眠・覚醒の安定化機構と行動制御 (2009)
  • Author(s): 桜井武
  • Organizer: 北陸実験動物研究会
  • Place of Presentation: 金沢
  • Year and Date: 2009-04-18
• [Presentation] 新規神経ペプチドの探索とその機能解析 (2009)
  • Author(s): 桜井武
  • Organizer: フォーラム富山第27回研究会
  • Place of Presentation: 富山
  • Year and Date: 2009-02-10
• [Presentation] 睡眠・覚醒と情動における新規神経ペプチドの役割 (2009)
  • Author(s): 桜井武
  • Organizer: 第7回北海道大学脳科学研究教育センターシンポジウム「脳の個性を科学する:遺伝子と環境がつくる脳の力」
  • Place of Presentation: 金
• [Presentation] a neuropeptide at the interface of emotion, metabolism and sleep/wake states. (2009)
  • Author(s): Sakurai, T. Orexin
  • Organizer: Satellite Symposium of the 9th International Symposium on VIP, PACAP and Related Peptide
  • Place of Presentation: Yakushima, Kagoshima
• [Presentation] 新規神経ペプチドと覚醒・情動 (2009)
  • Author(s): 桜井武
  • Organizer: 第27回内分泌代謝学サマーセミナー
  • Place of Presentation: 福井
• [Presentation] Speaker in the 3rd annual symposium of Japanese-French Frontiers of Science (2009)
  • Author(s): Sakurai, T
  • Place of Presentation: Kanagawa, Japan
• [Presentation] Orexin : a neuropeptide at the interface of emotion, metabolism and sleep/wake states. (2009)
  • Author(s): Sakurai, T
  • Organizer: Satellite Symposium of the 9^<th> International Symposium on VIP, PACAP and Related Peptide
  • Place of Presentation: 屋久島いわさきホテル、(鹿児島)
• [Presentation] Acute and Chronid Regulation of Sleep-Wakefulness States by Orexin/Hypocretin Neurons (2008)
  • Author(s): Sakurai, T
  • Organizer: SfN meeting
  • Place of Presentation: ワシントンD.C.(米国)
  • Year and Date: 2008-11-14
• [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 An nual Meeting of JSBP
  • Place of Presentation: 富山
  • Year and Date: 2008-09-12
• [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: オウル(フィンランド)
  • Year and Date: 2008-08-13
• [Presentation] Acute and Chronic Regulation of Sleep-Wakefulness States by Orexin/ Hypocretin (2008)
  • Author(s): Sakurai, T
  • Organizer: 22^<nd> APSS annual meeting
  • Place of Presentation: ボルチモア(米国)
  • Year and Date: 2008-06-10
• [Presentation] Orexin (Hypocretin) gene transfer improves narcoleptic symptoms in orexin null mice (2008)
  • Author(s): Liu, M, et.al.
  • Organizer: 22^<nd> APSS annual meeting
  • Place of Presentation: ボルチモア(米国)
  • Year and Date: 2008-06-10
• [Presentation] Entrainment of Temperature and Activity Rhythms to Restricted Feeding in Orexin Knock Out Mice (2008)
  • Author(s): Kaur S., et.al.
  • Organizer: 22^<nd> APSS annual meeting
  • Place of Presentation: ボルチモア(米国)
  • Year and Date: 2008-06-07
• [Presentation] Acute and Chronic Regulation of Sleep-Wakefulness States by Orexin/Hypocretin Neurons. (2008)
  • Author(s): Sakurai, T
  • Organizer: SfN meeting
  • Place of Presentation: Washington D.C., USA
• [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
• [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
• [Presentation] Acute and Chronic Regulation of Sleep-Wakefulness States by Orexin/Hypocretin Symposium S02 at Sleep2008 (2008)
  • Author(s): Sakurai, T.
  • Organizer: 22nd APSS annual meeting
  • Place of Presentation: Baltimore, MD, USA
• [Book] Orphan G protein-coupled receptors and novel neuropeptides. Orexins and Orexin Receptors : From Molecules to Integrative Physiology (2008)
  • Author(s): Matsuki T and Sakurai T
  • Total Pages: 256
  • Publisher: Springer
• [Book] The NPB/NPW Neuropeptide System and Its Role in Regulating Energy Homeostasis, Pain, and Emotion (2008)
  • Author(s): Hondo M., Ishii, M. and Sakurai T
  • Total Pages: 256
  • Publisher: Springer
• [Book] 脳と栄養ハンドブック (2008)
  • Author(s): 桜井武
  • Total Pages: 330
  • Publisher: サイエンスフォーラム社
• [Book] 時間生物学辞典 (2008)
  • Author(s): 桜井武
  • Total Pages: 340
  • Publisher: 朝倉書店
• [Book] 臨床睡眠学 (2008)
  • Author(s): 桜井武
  • Total Pages: 470
  • Publisher: 日本臨床社
• [Remarks]
  • URL: http://web.kanazawa-u.ac.jp/~med05/