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

Expression of clock genes in human peripheral blood mononuclear cells throughout the sleep/wake and circadian cycles
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DOI:
10.1080/07420520701800736
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发表时间:
2007-01-01
影响因子:
2.8
通讯作者:
Cermakian, Nicolas
Cermakian, Nicolas
中科院分区:
医学4区
文献类型:
--
作者:
James, Francine O.;Boivin, Diane B.;Cermakian, Nicolas

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生物钟基因在视交叉上核(SCN)神经元中的节律性表达是内源性昼夜节律在行为和生理上的表现。最近的证据表明,在非SCN组织中的节律时钟基因表达表明,功能时钟存在于大脑的中央昼夜节律起搏器之外。在这项调查中,在外周血单核细胞(PBMC)的振荡器的性质进行评估,通过评估时钟基因表达在整个一个典型的睡眠/觉醒周期(LD),并在一个恒定的常规(CR)。6名年龄(平均值+/- SEM)为23.7 +/- 1.6岁的健康男性和女性参与了这项为期5天的暂时隔离研究。测量核心体温和血浆褪黑激素浓度作为中枢昼夜节律起搏器的标志。在整个不间断的72小时期间采样的PBMC中定量HPER 1、HPER 2和HBMAL 1的表达。在CR期间测量的核心体温最低值和褪黑激素浓度的中点分别发生在习惯性觉醒前2:17 +/- 0:20和3:24 +/- 0:09 h,并且与睡眠/觉醒周期完全一致。PBMC中的HPER 1和HPER 2表达表现出显著的昼夜节律性,在清醒时间后早期达到峰值,并且在LD和CR条件下相当。HBMAL 1的表达变化更大,在LD条件下在清醒期中期达到峰值,在CR条件下在习惯性睡眠期达到峰值。对于第一次,连续三天的双小时采样被用来比较在不同的睡眠/觉醒条件下的人类外周振荡器中的时钟基因表达。
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.