2004 Fiscal Year Final Research Report Summary
Molecular Analysis of the sleep and arousal regulations and their relationship to the circadian rhythm using fruit fly, Drosophila melanogaster.
| Project/Area Number |
15300108
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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 |
Neuroscience in general
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| Research Institution | Kumamoto University |
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Principal Investigator |
KUME Kazuhiko Kumamoto University, Institute of Molecular Embryology and Geneticys, Associate Professor, 発生医学研究センター, 助教授 (30251218)
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| Co-Investigator(Kenkyū-buntansha) |
KUME Shoen Kumamoto University, Institute of Molecular Embryology and Geneticys, Professor, 発生医学研究センター, 教授 (70347011)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Drosophila / chronobiology / sleep / insomnia / dopamine / longevity / biological clock / circadian rhythm |
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| Research Abstract |
Physiologically, sleep is defined by electroencephalography, and typical REM and NREM sleep occur only in mammalian and avian species. But sleep-like inactive states also appear in other vertebrates and even in invertebrates. Similar to mammalian sleep, the inactive 'rest' state of insect is regulated by both circadian and homeostatic processes, which were demonstrated first in the cockroach 1, then in the fruit fly, Drosophila melanogaster. However, the similarity is based primarily on behavioral criteria.
In the course of analyzing the nature of sleep-like rest behavior in Drosophila, we discovered by serendipity hyperactive sleepless mutant flies and named them fumin (fmn), which means 'sleepless' in Japanese. We then determined the nature of the mutation by forward genetics. To our surprise, we found that their behavioral phenotype is due to a genetic lesion in the dopamine transporter (DAT) gene. The elimination of DAT activity generates a continuous wakefulness in mutant flies, resulting in dramatically increased activity levels. finn mutants are more sensitive to mechanical stimuli when they are in prolonged immobility, indicating their decreased arousal threshold. They also show attenuations in rest (sleep) rebound.
Mammalian DAT is a well-known target of psychostimulants, such as amphetamine and cocaine, and involved in wakefulness regulations. These results indicate a critical role of dopamine for arousal state in Drosophila and highlight a similarity between insects and mammals regarding the molecular basis of arousal. The use of a Drosophila model is expected to facilitate an understanding of arousal regulations.
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