| Project/Area Number |
18603002
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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 |
睡眠学
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
HONDA Kazuki Tokyo Medical and Dental University, Institute of Biomaterials and Bioengineering, Professor (70173656)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAI Keiji Tokyo Medical and Dental University, 難治疾患研究所, 准教授 (70156628)
片山 芳文 東京医科歯科大学, 難治疾患研究所, 教授 (20014144)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Sleep disorder / Non-REM sleep / REM sleep / Food intake / Motilin / Ghrelin / Orexin / Parkinson's Disease / ドパミン / ナルコレプシー / オレキシン / ドーパミン |
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| Research Abstract |
In recent decades, many of the chemical and neuronal substrates involved in sleep-wake regulation have been identified. Recently, orexins A and B involved in the regulation of the feeding and arousal states, were identified. An intracerebroventricular (icv) infusion of both orexins A and B has been observed to induce arousal effects in rats. In the present studies, we investigated the involvement of humoral factors in neurophysiological regulation of sleep-wake states and animal models for sleep research.
1. An icv infusion of orexin A for a 5-h period markedly increased the amount of wakefulness over the baseline value. OX2R antagonist decreased orexin A-induced wakefulness. Although OX2R antagonist treatment alone slightly changed each sleep parameter, no significant difference was observed. Pretreatment with OX2R antagonist, significant inhibited orexin A-induced wakefulness in rats. The finding this study therefore suggest that OX2R involved in arousal state regulation.
2. Motilin is known to regulate the feeding system. We investigated the effects of icv infusion of motilin (1, 10, 50, 100 nml) on the sleep-waking cycle in the freely behaving rats. Motilin at the dose of 100 nmol markedly increased the amount of wakefulness by 75.0% (p<0.05) over the baseline value. These finding suggest that motilin also modulates sleep-wake states and behavioral responses.
3. Parkinson's Disease (PD) is a progressive neurodegenerative disease wherein dopaminergic neuron in the substantia nigra pars compacta (SNpc) are destroyed. In this study, α-synuclein transgenic (TG) mice for the diminished expression of dopaminergic neurons in SNpc were used to investigate sleep architecture, and compared to wild type (WT) mice. Analysis of sleep architecture had no significant differences between TG and WT mice. Further research on the influence of the dopaminergic system on the sleep-wake cycle using PD models is needed to validate the observed sleep-wake cycle disturbances.
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