2002 Fiscal Year Final Research Report Summary
STUDY ON MECHANISM AND TREATMENT OF JET LAG CAUSED BY DISSOCIATION OF TWO OSILLATORS.
| Project/Area Number |
13557007
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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 | 展開研究 |
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| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | KINKI UNIVERSITY |
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Principal Investigator |
SHIGEYOSHI Yasufumi KINKI UNIVERSITY SCHOOL OF MEDICINE, Professor, 医学部, 助教授 (20275192)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAHAMA Ken-ichi KINKI UNIVERSITY SCHOOL OF MEDICINE, Assistant, 医学部, 助手 (60281515)
NAGANO Mamoru KINKI UNIVERSITY SCHOOL OF MEDICINE, Assistant, 医学部, 助手 (80155960)
FUJIOKA Atsuko KINKI UNIVERSITY SCHOOL OF MEDICINE, Assistant Professor, 医学部, 助教授 (30077664)
SATO Shinsuke KINKI UNIVERSITY SCHOOL OF MEDICINE, Assistant, 医学部, 助手 (40270574)
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| Project Period (FY) |
2001 – 2002
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| Keywords | INTERNAL CLOCK / CIRCADIAN RHYTHM / CLOCK GENES / Rev-erb / JET LAG / Per1 / cAMP / SUPRACHIASMATIC NUCLEUS |
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| Research Abstract |
A. Dichotomy of the circadian center is associated with jet lag syndrome
In both 10 hour delay and 6 hour advance of light-dark cycle, we found that there appeared the dissociation of the suprachiasmatic into two oscillators. The ventrolateral region of the SCN (VLSCN) shifted rapidly whereas the dorsomedial regions of the SCN (DMSCN) shifted very slowly, spent more than a week to regain synchronization of the VLSCN and VLSCN. The sluggish shift of the DMSCN corresponds to the suppressed locomotors activity, which suggests that jet lag is caused by the slow shift of the DMSCN after LD cycle shift.
B. Transgene of mammalian Per2 genes to Per2-null Drosophila mutants recovered the circadian rhythmicity.
We introduced transgene to Per2-null Drosophila of which activity is arrhythmic. In the Drosophila expressing mouse Per21 or Per22 gene, we found the recovery of locomotor rhythms. The finding suggests that Pa-21 and Per22 have similar roles of clock genes even in the mammalian species.
C. A Transcription Factor Response Element for Gene Eypressinn During Circadian Night
We profiled suprachiasmatic nuclei (SCN) and liver genome-wide expression patterns under light/dark (LD) cycles and constant darkness (DD). We extensively determined transcription start sites (TSS) of human orthologues for newly identified cycling genes and then Per2 formed bioinformatical searches for relationships between time-of-day specific expression and transcription factor response elements around TSS. We demonstrate the role of the Rev-ErbA/ROR response element in gene expression of nocturnally expressed genes in SCN and liver.
D. Phosphodiesterase type,4 (PDE4) specifically degradg cAMP
To enhance Per21 transcription by the inhibition of cAMP degradation, we used Rolipram, a specific inhibitor of phosphodiesterase type 4 which degrades the cAMP. We found that the Per21 transcript increased transiently but the Per2iod length of Per21 increase was not extended.
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[Publications] Ueda HR, Chen W, Adachi A, Wakamatsu H, Hayashi Sm Takasugi T, Nagano M, Nakahama K, Suzuki Y, Sugano S, Iino M, Shigeyoshi Y, Hashimoto S: "A transcription factor response element for gene expression during circadian night"Nature. 418(68979). 534-539 (2002)
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[Publications] Nakamura, T., Shigeyoshi, Y., Maebayashi, Y., Yamaguchi, S., Yagita, K., Okamura, H.: "Different developmental profiles of the expression of preprosomatostatin and preprotachykinin-A mRNAs in rat SCN neurons"Dev.Brain Research. 127. 81-86 (2001)
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「研究成果報告書概要(和文)」より
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[Publications] Ueda, H. U., Chen, W., Adachi, A., Wakamatsu, H., Hayashi, S., Takasugi, T., Nagano, N., Nakahama, K., Suzuki, Y., Sugano, S., Iino, M., Shigeyoshi. Y. and Hashimoto, S.: "A Transcription Factor Response Element for Gene Expression During Circadian Night."Nature. 418. 534-539 (2002)
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[Publications] Nakahama, K., Fujioka, A., Nagano, M., Satoh, S., Furukawa, K., Sasaki, H., and Shigeyoshi. Y.: "A role of the C-terminus of aquaporin 4 in its membrane pxpression in cultured astrocytes"Genes Cells. 7. 731-741 (2002)
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[Publications] Shigeyoshi. Y., Meyer-Bernstein, E., Yagita, K., Fu, W., Chen, Y., Takumi, T., Schotland, P., Sehgal, A., and Okamura, H: "Restoration of circadian behavioral rhythms in a period null Drosophila mutant (per01)by mammalian period homologues mPerl and mPer2."Genes Cells. 7. 163-171 (2002)
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[Publications] Taguchi, K., Okura, R., Yagita, K., Ishida, Y., Onishi, H., Shigeyoshi. Y., Yamaguchi. S., Nishimura, M., Masubuchi, S., and Okamura, H: "Different Circadian Expression Profiles of Clock Genes in the Mouse Suprachiasmatic Nuclues."Biomedical Journal. 22. 125-131 (2001)
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[Publications] Yamamoto, S., Shigeyoshi. Y., Ishida, Y., Fukuyama, T., Yamaguchi, S., Yagita, K., Moriya, Y., Shibata, S., Yakashima, N., and Okamura, H: "Expression of the Per1 gene in the Hamster: Brain Atlas and Circadian Characteristics in the Suprachiasmatic Nucleus."J. Comp. Neurol.. 430. 518-532 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Nakaniura, T., Shigeyoshi. Y., Maebayashi, Y., Yamagucni, S., Yagita, K., and Okamura, H,: "Different developmental profiles of the expression of preprosomatostatin and preprotachykinin-A mRNAs in rat SCN neurons."Dev. Brain Research. 127. 81-86 (2001)
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「研究成果報告書概要(欧文)」より
