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Expression of clock genes in human peripheral blood mononuclear cells throughout the sleep/wake and circadian cycles

机译:在整个睡眠/唤醒和昼夜周期中人外周血单个核细胞中时钟基因的表达

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The rhythmic expression of circadian clock genes in the neurons of the suprachiasmatic nucleus (SCN) underlies the manifestation of endogenous circadian rhythmicity in behavior and physiology. Recent evidence demonstrating rhythmic clock gene expression in non-SCN tissues suggests that functional clocks exist outside the central circadian pacemaker of the brain. In this investigation, the nature of an oscillator in peripheral blood mononuclear cells (PBMCs) is evaluated by assessing clock gene expression throughout both a typical sleep/wake cycle (LD) and during a constant routine (CR). Six healthy men and women aged (mean +/- SEM) 23.7 +/- 1.6 yrs participated in this five-day investigation in temporal isolation. Core body temperature and plasma melatonin concentration were measured as markers of the central circadian pacemaker. The expression of HPER1, HPER2, and HBMAL1 was quantified in PBMCs sampled throughout an uninterrupted 72 h period. The core body temperature minimum and the midpoint of melatonin concentration measured during the CR occurred 2:17 +/- 0:20 and 3:24 +/- 0:09 h before habitual awakening, respectively, and were well aligned to the sleep/wake cycle. HPER1 and HPER2 expression in PBMCs demonstrated significant circadian rhythmicity that peaked early after wake-time and was comparable under LD and CR conditions. HBMAL1 expression was more variable, and peaked in the middle of the wake period under LD conditions and during the habitual sleep period under CR conditions. For the first time, bi-hourly sampling over three consecutive days is used to compare clock gene expression in a human peripheral oscillator under different sleep/wake conditions.
机译:昼夜节律性神经元(SCN)神经元中节律性时钟基因的节律性表达是行为和生理学中内源性节律性节律性表现的基础。最近的证据表明,非SCN组织中节律性时钟基因的表达表明功能性时钟存在于大脑中央昼夜节律起搏器之外。在这项研究中,通过评估整个典型睡眠/唤醒周期(LD)和恒定程序(CR)中的时钟基因表达来评估外周血单核细胞(PBMC)中振荡器的性质。六名年龄在23.7 +/- 1.6岁(平均+/- SEM)的健康男女参加了为期五天的暂时性隔离调查。测量核心体温和血浆褪黑激素浓度,作为中央昼夜节律起搏器的标志物。在整个不间断的72小时内,对PBMC中HPER1,HPER2和HBMAL1的表达进行定量。 CR期间测得的核心体温最低值和褪黑激素浓度中点分别发生在习惯性觉醒之前的2:17 +/- 0:20和3:24 +/- 0:09 h,并与睡眠/唤醒周期。 PBMC中的HPER1和HPER2表达表现出明显的昼夜节律,在苏醒时间后达到峰值,在LD和CR条件下相当。 HBMAL1表达更具可变性,并在LD条件下的醒来中期和CR条件下的习惯性睡眠期达到峰值。首次连续三天每两小时采样一次,用于比较不同睡眠/唤醒条件下人类外围振荡器中的时钟基因表达。

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