| Project/Area Number |
01440026
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Osaka Bioscience Institute |
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Principal Investigator |
HAYAISHI Osamu Osaka Bioscience Institute, Director, 所長 (40025507)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Yasuyoshi Osaka Bioscience Institute, 3rd Dept., Head, 第3研究部, 部長 (40144399)
MATSUMURA Hitoshi Osaka Bioscience Institute, 2nd Dept., Vice-Head, 第2研究部, 研究副部長 (50173886)
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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1991: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1990: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Keywords | Prostaglandin / Sleep / Wakefulness / Antagonist / Hemoglobin / PGD synthase inhibitor / Selenium / Neuron / 冬眠 / 睡眠・覚醒 / マイクロダイアリシス / セレニウム / 2ーdeoxyglucose / 断眠 / プロスタグランジンE_2 / プロスタグランジンD_2 / 視束前野 / 視床下部 |
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| Research Abstract |
Studies on molecular mechanisms of sleep-wake regulation were conducted in rats and monkeys. Significant findings were,
1. Inorganic selenium compounds such as SeCl_4 and Na_2SeO_3 inhibited the activity of prostaglandin (PG) D synthase of the rat brain. These compounds markedly inhibited sleep of rats when administered into the third cerebral ventricle. Excess amount of dithiothreitol blocked the inhibition of PGD synthase activity as well as the inhibition of sleep by selenium. These results indicate that PGD_2 synthesized in the brain tissue is involved in the promotion of physiological sleep. Intravenous infusion of these selenium compounds also inhibited sleep of rats, suggesting that these selenium compounds can be used clinically for the therapy of some diseases categorized in hypersomnia disorders.
2. AH 6809, an antagonist of PGE_2, inhibited the awaking effect of PGE_2 in rats without altering the hyperthermic effect of PGE_2. Intracerebroventricular infusion of AH 6809 alone suppressed wakefulness and increased sleep. These results suggest that the subtype of PGE_2 receptors for the awaking effect is different from the subtype for hyperthermic effect, and that PGE_2 produced physiologically in the brain is involved in the promotion and maintenance of wakefulness.
3. In the hypothalamus of rats, there are neurons which change their activities along with the alterations of sleep-wake states and respond specifically to the application of PGD_2 or PGE_2. It is conceivable that PGD_2 and PGE_2 are regulating sleep-wake activities, at least in part, by acting as neuromodulators on these neurons. The distribution of these neurons in the hypothalamus was also examined.
4. The oxygenation state of hemoglobin in the monkey forebrain was monitored continuously using a near-infrared spectrophotometric technique. It is suggested that oxygen consumption decreases specifically during REM sleep.
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