| Project/Area Number |
17590183
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Chiba University |
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Principal Investigator |
FUKUDA Yasuichiro Chiba University Graduate School of Medicine, Department of Autonomic Physiology, Professor, 大学院医学研究院, 教授 (10009649)
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| Co-Investigator(Kenkyū-buntansha) |
KUWAKI Tomoyuki Chiba University Graduate School of Medicine, Department of Molecular & Integrative Physiology, Professor, 大学院医学研究院, 教授 (80205260)
SHIMOYAMA Megumi Chiba University Graduate School of Medicine, Department of Autonomic Physiology, Assistant Professor, 大学院医学研究院, 講師 (10206253)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Respiraoty regulation / Vigilance state / Orexin / Chemoreceptor reflex / Knockout mice / Orexin receptor antagonist / International information exchange / U.S.A. / ノツクアウトマウス |
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| Research Abstract |
[Purpose] Respiratory regulation depends on the vigilance state. We examined whether orexin contribute to the underlying mechanism.
[Methods] 1) Effect of intracerebroventricular administration of orexin on cardiorespiratory parameters in anesthetized mice was examined. 2) In freely moving orexin knockout mice (KO) and wild type (WT) controls, ventilation was measured for 6 hrs by whole body plethysmography together with EEG and EMG. Effect of inspired gas composition (room air, hypercapnic, or hypoxic gas mixtures) on ventilation was separately examined during sleep and wake periods. 3) In a similar experimental setup, effect of administration of orexin agonist and antagonist was examined using KO and WT.
[Results] 1) Intracerebroventricular administration of orexin increased blood pressure, heart rate, and respiration. Effect on respiration was greater than that on cardiovascular parameters. 2) Although basal respiration during wake and sleep periods was' comparable between KO and WT, hypercapnic chemoreflex in KO was specifically blunted during wake but not sleep period. Hypoxic chemoreflex in KO was normal. In addition, sleep apnea was augmented in KO. 3) Supplementation of orexin-A and orexin-B partially but significantly increased hypercapnic chemoreflex in KO. On the contrary, administration orexin receptor antagonist in WT significantly attenuated hypercapnic chemoreflex.
[Discussion and Conclusion] These data collectively support our hypothesis that orexin serves-as a vigilance state-dependent neuromodulator of the respiratory regulation.
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