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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.昼夜节律中心的二分法与时差综合症有关在明暗周期延迟10小时和提前6小时后，观察到视交叉上核（昼夜节律中心）分离成两个振荡器。 SCN的腹外侧区（VLSCN）移动迅速，而SCN的背内侧区（DMSCN）移动缓慢，花了一周多的时间才恢复VLSCN和DMSCN的同步。 DMSCN 的缓慢变化与主观夜间运动活动的抑制相对应，这表明时差是由 LD 周期变化后 DMSCN 的缓慢变化引起的。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）循环和持续黑暗（DD）下的视交叉上核（SCN）和肝脏全基因组表达模式。我们确定了新鉴定的循环基因的人类直向同源物的转录起始位点（TSS），然后进行生物信息学搜索，以寻找一天中的时间特异性表达与 TSS 周围转录因子反应元件之间的关系。我们证明了Rev-ErbA/ROR反应元件在SCN和肝脏夜间表达基因的基因表达中的作用。3.4型磷酸二酯酶(PDE4)特异性降解cAMP为了通过抑制cAMP降解来延长Per1的表达，我们使用了Rolipram，一种4型磷酸二酯酶的特异性抑制剂，它降解cAMP。应用咯利普兰后，Perl 转录物的数量短暂增加，但 Perl 诱导的时间长度并未延长。