STUDY ON MECHANISM AND TREATMENT OF JET LAG CAUSED BY DISSOCIATION OF TWO OSILLATORS.

两个振荡器分离所致时差反应的机理及治疗研究。

基本信息

批准号：
13557007
负责人：
SHIGEYOSHI Yasufumi
金额：
$ 1.09万
依托单位：
KINKI UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557007/
关键词：
INTERNAL CLOCK CIRCADIAN RHYTHM CLOCK GENES Rev-erb JET LAG Per1 cAMP SUPRACHIASMATIC NUCLEUS 慨日周期位相変位

项目摘要

A. Dichotomy of the circadian center is associated with jet lag syndromeIn 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 NightWe 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 cAMPTo 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.

A.昼夜节律中心的二分法与喷气滞后综合征蛋白延迟10小时，并在光黑暗周期前6小时相关，我们发现肩so骨上的分离成两个振荡器。 SCN（VLSCN）的腹外侧区域迅速移动，而SCN（DMSCN）的背侧区域非常缓慢地移动，花费了一个多星期来恢复VLSCN和VLSCN的同步。 DMSCN的缓慢移位对应于受抑制的运动活性，这表明射流滞后是由LD循环偏移后DMSCN的缓慢移动引起的。哺乳动物PER2基因的转基因对Per2-null果蝇突变体恢复了昼夜节律。我们将转基因引入了per2-null果蝇，其活性是心律不齐的。在表达小鼠PER21或PER22基因的果蝇中，我们发现了运动节奏的恢复。该发现表明，即使在哺乳动物物种中，PA-21和PER22也具有相似的时钟基因作用。昼夜节日期间基因e-eypressinn的转录因子响应元件介绍了在光/黑暗（LD）周期和恒定黑暗（DD）下的核核（SCN）和全肝基因组表达模式。我们为新鉴定的循环基因的人类直系同源物的广泛确定了转录起始位点（TSS），然后PER2形成了生物信息性搜索，以搜索TSS周围的日期特定表达和转录因子响应元素之间的关系。我们证明了Rev-Erba/ROR反应元件在SCN和Liver.d中夜间表达基因的基因表达中的作用。磷酸二酯酶类型，4（PDE4）特异性降解campto通过抑制营地降解增强了PER21转录，我们使用了Rolipram，Rolipram是磷酸二酯酶4型的特定抑制剂，使CAMP降解。我们发现PER21转录本瞬时增加，但PER2IOD长度的增加并未延长。