Diversity of mode of human circadian signal transmission in young and elderly subjects

年轻和老年受试者人体昼夜节律信号传输模式的多样性

基本信息

批准号：
15390347
负责人：
MISHIMA Kazuo
金额：
$ 7.87万
依托单位：
Akita University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

The aim of the present study is to investigate the properties of human circadian signal transmission and influence of aging on the humoral/neuronal signal transmission and their reciprocal phase relationship. We firstly established measuring method for expression analysis of 10 circadian clock genes including hPer1, hPer2, hPer3, Clock, BMAL1, Timeless, Cry1, Cry2, Dec1, Dec2 in peripheral mononuclear cells (MNCs) and polymorphonuclear neutrophils (PMNs) as a model of humoral circadian transmission in healthy young male volunteers. We obtained blood samples every 2 hours under modified constant routine conditions, and extracted mRNA for real-time quantitative PCR analysi using TaqMan fluorogenic probes and corresponding primer sets. We detected significant expression all of the 10 circadian clock genes in both the MNCs and PMNs. Gene expression of hPer1, hPer2, hPer3, Cry1, Cry2, Dec1, Dec2 in MNCs and PMNs showed significant daily variations, while Clock showed no significant circadia … More n variation as described in the suprachiasmatic nucleus (SCN), the circadian master clock, and peripheral tissues in nocturnal animals. Additionally, hPer1, hPer2, hPer3 showed similar acrophases and peak transcription in the transition period from subjective night to subjective day (early subjective morning). Especially, the acrophases in hPer1 expression rhythms in MNCs and PMNs were found to correlate positively with that of the serum melatonin secretion rhythms, which is a reliable phase marker of the SCN. The present findings indicate that clock gene activity could be preserved across different peripheral blood cell types and support the assumption that peripheral clocks are entrained by the SCN. There were no significant differences in hPer1, hPer2, hPer3 expression in MNCs between healthy young and 60s elderly subjects. This suggests that ability of entrainment of peripheral clocks to the circadian humoral signals oscillating from the SCN is maintained at least in the healthy elderly subjects until 60s under entrained condition. Conversely, we observed internal desynchronization among body temperature, melatonin, cortisol and hPer gene family expression rhythms showing different free-running periods in non-24 sleep-wake rhythm patients. These findings suggest diversity of mode of circadian humoral/neuronal signal transmission in humans. Less

本研究的目的是研究人类昼夜信号传播的特性以及衰老对体液/神经元信号传递及其相互相关的影响。我们首先建立了对10个昼夜节律钟基因表达分析的测量方法，包括HPER1，HPER2，HPER3，CHICK，BMAL1，NEMELLE，CRY1，CRY1，CRY2，DEC1，DEC1，DEC2，单核细胞（MNC）和多伴有神经性恋爱的神经性神经性神经性（PMN）（PMNS），作为一个健康的男性传播典型的型号。我们在修改的恒定常规条件下每2小时获得每2小时的血液样本，并提取mRNA，以使用Taqman荧光问题和相应的引物组分析实时定量PCR。我们在跨国公司和PMN中检测到了所有10个昼夜节律基因的显着表达。 HPER1，HPER2，HPER3，CRY1，CRY2，DEC1，DEC2的基因表达在MNC和PMN中显示出显着的每日变化，而时钟没有显着的Circadia……如上图中核核（SCN）所述的N变化更多的N变化，昼夜节律大师时钟和Nocturnnurnnal动物的外围组织。此外，HPER1，HPER2，HPER3在从主观夜晚到主观的日（主观早晨）的过渡期都显示出相似的萎缩和峰值转录。尤其是，发现MNC和PMN中HPER1表达节奏中的谷物相与血清褪黑激素分泌节律的正相关，这是SCN的可靠相标记。目前的发现表明，时钟基因活性可以在不同的外周血细胞类型中保存，并支持外周钟由SCN累积的假设。 HPER1，HPER2，HPER3在健康的年轻人和60年代的受试者之间没有显着差异。这表明，从SCN振荡的昼夜节律信号的外围时钟的入围能力至少在健康的受试者中一直保持在健康的受试者中，直到60年代在入围条件下。相反，我们观察到体温，褪黑激素，皮质醇和HPER基因家族表达节律之间的内部对同步，在非24个睡眠节奏患者中显示出不同的自由运行时期。这些发现表明人类昼夜节律/神经元信号传播的多样性。较少的