Discovery of molecular mechanisms of identified cycling genes using a gene chip in the suprachiasmatic nucleus

使用视交叉上核中的基因芯片发现已识别循环基因的分子机制

基本信息

批准号：
15590178
负责人：
NAGANO Mamoru
金额：
$ 1.98万
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：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590178/
关键词：
SUPRACHIASMATIC NUCLEUS CIRCADIAN RHYTHM IN SITU HYBRIDIZATION ID2 GENE HSP GENE PHOTIC ENTRAINMENT 体内時計 Id2 遺伝子

项目摘要

We identified cycling 101 genes in the suprachiasmatic nucleus(SCN) using a gene chip. Next, using in situ hybridization, we examined whether these genes expresses rhythmically or not in the SCN and detected rhythmic expression of some genes. The SCN showed oscillatory expression of ID2 in both LD and DD, high during the night, low during the day. We suggested that ID2 works as a negative regulator of the transcription and may be good candidate for the modulator of Per transcription.In addition, Dexras1 and HSPa5 mRNA expression showed circadian rhythm, peaked during night and these genes expression were found predominantly in the dorsomedial portion of the SCN(DMSCN).We investigated expression profiles of Per genes in the rat SCN in steady light-dark condition by in situ hybridization method, with special reference to the induction in the ventrolateral portion of the SCN(VLSCN). In the LD condition, the onset of the Pen and Per2 genes expression in the SCN began 30 minutes after lights on, while the VLSCN did not expression Per genes until 2hours after lights on in DD. Therefore, it is likely that the expression of Per genes during the early daytime is caused by the exposure to light during subjective night. These findings suggest that the involvement of Per genes in the daily synchronization of the circadian clock to environment time. Also, we demonstrate that an abrupt shift in the LD cycle disrupts the synchronous oscillation of circadian components in the rat SCN. The VLSCN, photoreceptive region, shifted rapidly, but the DMSCN were relatively slow to shift. This dissociation and slow resynchronization of endogenous oscillators within the SCN after an LD cycle shift suggests a mechanism for the physiological symptoms that constitute jet lag. Then these finding suggested that there are potential two oscillators in the SCN.

我们使用基因芯片鉴定了超平性核（SCN）中的101个基因。接下来，使用原位杂交，我们检查了这些基因在SCN中是否有节奏表达，并检测到某些基因的节奏表达。 SCN在LD和DD中均显示ID2的振荡表达，夜晚高，白天低。我们建议ID2作为转录的负调节剂，可能是每次转录调节剂的良好候选者。此外，DexRAS1和HSPA5 mRNA表达表现出昼夜节律，在夜间达到峰值，这些基因表达在SCN中的稳定范围中均可在表达中进行均匀的调节。杂交方法，特别提及SCN（VLSCN）的腹外侧部分的诱导。在LD状态下，pen和PER2基因在SCN中的表达开始后30分钟开始，而VLSCN直到在DD中亮起后2小时才能每个基因表达。因此，早期日期中每个基因的表达可能是由主观夜晚的光暴露引起的。这些发现表明，每个基因参与昼夜节律时钟与环境时间的每日同步。另外，我们证明LD循环的突然转移破坏了大鼠SCN中昼夜节律成分的同步振荡。 VLSCN（感光区域）迅速移动，但DMSCN的移位速度相对较慢。 LD周期转移后SCN内的内源振荡器的这种解离并缓慢重新同步，这表明了构成喷气滞后的生理症状的机制。然后这些发现表明SCN中有两个潜在的振荡器。