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IN SEARCH OF THE COUSE AND TREAMENT FOR JETLAG

寻找时差的方法和治疗方法

基本信息

批准号：
14570071
负责人：
SHIGEYOSHI Yasufumi
金额：
$ 2.24万
依托单位：
KINKI UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570071/
关键词：
SUPRACHIASMATIC NUCLEUS DESYNCHRONY ETLAG JETLAG SYNDROME CIRCADIAN RHYTHM GENEME Per1 INTTERNAL CLOCK Perl Per2 Cry1 Rev-erb Gene Chip

项目摘要

1.Dichotomy of the circadian center is associated with jet lag syndromeDissociation of the suprachiasmatic nucleus, the circadian center, into two oscillators was observed after 10 hour delay and 6 hour advance of light-dark cycle. The ventrolateral region of the SCN(VLSCN) shifted rapidly whereas the dorsomedial regions of the SCN(DMSCN) shifted slowly, spent more than a week to regain synchronization of the VLSCN and DMSCN. The sluggish shift of the DMSCN corresponded to the suppressed locomotors activity during the subjective night, which suggested that jet lag was caused by the slow shift of the DMSCN after LD cycle shift.2.A Transcription Factor Response Element for Gene Expression During Circadian NightWe profiled suprachiasmatic nuclei(SCN) and liver genome-wide expression patterns under light/dark(LD) cycles and constant darkness(DD). We determined transcription start sites(TSS) of human orthologues for newly identified cycling genes and then performed 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.3.Phosphodiesterase type 4(PDE4) specifically degrade cAMPTo elongate Per1 expression by the inhibition of cAMP degradation, we used Rolipram, a specific inhibitor of phosphodiesterase type 4, which degrades the cAMP. With Rolipram application, the amount of Perl transcripts increased transiently but the period length of Perl induction was not extended.

1.昼夜节律中枢的二分性与时差综合征有关在光暗周期延迟10小时和提前6小时后，观察到作为昼夜节律中枢的视交叉上核分裂为两个振荡器。SCN的腹外侧区（VLSCN）移动迅速，而SCN的背内侧区（DMSCN）移动缓慢，需要一周以上的时间才能恢复VLSCN和DMSCN的同步。DMSCN的缓慢移动对应于主观夜间运动活动的抑制，这表明时差是由LD周期转换后DMSCN的缓慢移动引起的。2.昼夜节律夜间基因表达的转录因子响应元件我们分析了光/暗（LD）周期和恒定黑暗（DD）下的视交叉上核（SCN）和肝脏全基因组表达模式。我们确定了新发现的循环基因的人类直系同源物的转录起始位点（TSS），然后进行生物信息学搜索，以了解TSS周围的时间特异性表达和转录因子响应元件之间的关系。我们证明了Rev-ErbA/ROR反应元件在SCN和肝脏中转录表达基因的基因表达中的作用。3.磷酸二酯酶4型（PDE 4）特异性降解cAMP为了通过抑制cAMP降解来延长Per 1的表达，我们使用了Rolipram，一种特异性磷酸二酯酶4型抑制剂，它降解cAMP。施用Rolipram后，Perl转录物的数量短暂增加，但Perl诱导期没有延长。