Study of the mechanisms that regulate the activity of orexin-producing neuron.
| Project/Area Number |
14370029
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
SAKURAI Takeshi University of Tsukuba, Graduate School of Comprehensive Human Sciences, Associate Professor, 大学院・人間総合科学研究科, 助教授 (60251055)
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| Co-Investigator(Kenkyū-buntansha) |
後藤 勝年 筑波大学, 基礎医学系, 教授 (30012660)
山中 章弘 筑波大学, 基礎医学系, 講師 (60323292)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥8,600,000 (Direct Cost: ¥8,600,000)
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| Keywords | orexin / arousal / narcolepsy / acetylcholine / serotonin / adaptive behavior / レプチン / グレリン / グルコース / エネルギーバランス |
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| Research Abstract |
The implication of orexin in narcolepsy suggests the importance of orexin in the normal regulation and maintenance of vigilance states. Orexin neurons project from the LHA to the monoaminergic and cholinergic nuclei in the brainstem to regulate sleep/wakefulness states as well as feeding. The activity of orexin neurons is inhibited by glucose and leptin, and stimulated by ghrelin. In accordance with the previous report that prepro-orexin mRNA is up-regulated by fasting, this observation suggests that orexin neurons sense the animal's nutritional state by monitoring humoral factors such as leptin and glucose. We also found that orexin neurons are inhibited by serotonin and noradrenaline, while excited by acetylcholine. We recently found that orexin neurons are innervated by multiple specific brain regions implicated in the regulation of sleep/wakefulness states. This study revealed that orexin neural network ensures"flip-flop"mechanisms between the POA sleep-active neurons and monoaminergic neurons. Thus, orexin neurons have functional interactions with hypothalamic feeding pathways and monoaminergic/cholinergic centers, and provide a critical link between peripheral energy balance and the CNS mechanisms that coordinate sleep/wakefulness and motivated behavior such as food seeking.
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Report
(4 results)
Research Products
(51 results)
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[Journal Article] Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in mice.2005
Author(s)
Sakurai T, Nagata R, Yamanaka A, Kawamura H.Tsujino N, Muraki Y, Kageyama H, Kunita S, Takahashi S, Goto K, Koyama Y, Shioda S, Yanagisawa M
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Journal Title
Neuron. 46(2)
Pages: 297-308
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in mice.2005
Author(s)
Sakurai T, Nagata R, Yamanaka A, Kawamura H, Tsujino N, Muraki Y, Kageyama H, Kunita S, Takahashi S, Goto K, Koyama Y, Shioda S, Yanagisawa M.
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Journal Title
Neuron. 46(2)
Pages: 297-308
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Orexins (hypocretins) directly interact with neuropeptide Y, POMC and glucose-responsive neurons to regulate Ca 2+ signaling in a reciprocal manner to leptin : orexigenic neuronal pathways in the mediobasal hypothalamus.2004
Author(s)
Muroya S, Funahashi H, Yamanaka A, Kohno D, Uramura K, Nambu T, Shibahara M, Kuramochi M, Takigawa M, Yanagisawa M, Sakurai T
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Journal Title
Eur.J.Neurosci. 19(6)
Pages: 1524-1534
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity.2004
Author(s)
Thompson MD, Comings DE, Abu-Ghazalah R, Jereseh Y, Lin L, Wade J, Sakurai T, Tokita S, Yoshida T, Tanaka H, Yanagisawa M, Burnham WM, Moldofsky H.
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Journal Title
Am.J.Med.Genet. 129B(1)
Pages: 69-75
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Orexins (hypocretins) directly interact with neuropeptide Y, POMC and glucose-responsive neurons to regulate Ca 2+ signaling in a reciprocal manner to leptin : orexigenic neuronal pathways in the mediobasal hypothalamus.2004
Author(s)
Muroya S, Funahashi H, Yamanaka A, Kohno D, Uramura K, Nambu T, Shibahara M, Kuramochi M, Takigawa M, Yanagisawa M, Sakurai T, Shioda S, Yada T.
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Journal Title
Eur J Neurosci. 19(6)
Pages: 1524-1534
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity.2004
Author(s)
Thompson MD, Comings DE, Abu-Ghazalah R, Jereseh Y, Lin L, Wade J, Sakurai T, Tokita S, Yoshida T, Tanaka H, Yanagisawa M, Burnham WM, Moldofsky H.
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Journal Title
Am J Med Genet. 129B(1)
Pages: 69-75
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Ghrelin-food intake is mediated via the orexin pathway.2003
Author(s)
Toshinai K, Date Y, Murakami N, Shimada M, Mondal MS, Shimbara T, Guan JL, Wang QPinduced, Funahashi H, Sakurai T, Shioda S, Matsukura S, Kangawa K, Nakazato M.
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Journal Title
Endocrinology 144(4)
Pages: 1506-1512
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Characterization of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8.2003
Author(s)
Tanaka H, Yoshida T, Miyamoto N, Motoike T, Kurosu H, Shibata K, Yamanaka A, Williams SC, Richardson JA, Tsujino N, Garry MG, Lerner MR, King DS, O'Dowd BF, Sakurai T. Yanagisawa M.
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Journal Title
Proc.Natl.Acad.Sci.USA. 100(10)
Pages: 6251-6256
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Hypothalamic Orexin neurons regulate arousal according to energy balance in mice.2003
Author(s)
Yamanaka A., Beuckmann CT., Willie JT., Hara J., Tsujino N., Mieda M., Tominaga M., Yagami K., Sugiyama F., Goto K., Yanagisawa M., Sakurai T.
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Journal Title
Neuron. 38
Pages: 701-713
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Characterization of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8.2003
Author(s)
Tanaka H, Yoshida T, Miyamoto N, Motoike T, Kurosu H, Shibata K, Yamanaka A, Williams SC, Richardson JA, Tsujino N, Garry MG, Lerner MR, King DS, O'Dowd BF, Sakurai T, Yanagisawa M.
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Journal Title
Proc Natl Acad Sci USA. 100(10)
Pages: 6251-6256
Description
「研究成果報告書概要(欧文)」より
Related Report
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