Expression of Clock Genes in Human Peripheral Blood Mononuclear Cells throughout the Sleep/Wake and Circadian Cycles

Dec 14, 2007Chronobiology international

Changes in body clock genes in human blood cells during sleep and daily cycles

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Abstract

Significant circadian rhythmicity of HPER1 and HPER2 expression in peripheral blood mononuclear cells was observed, peaking early after wake-time.

Core body temperature minimum and midpoint of plasma melatonin concentration were measured at 2:17±0:20 and 3:24±0:09 hours before habitual awakening, respectively.
Clock gene expression was assessed in peripheral blood mononuclear cells during both a typical sleep/wake cycle and a constant routine.
HPER1 and HPER2 expression patterns were consistent across different conditions, indicating they may function as peripheral oscillators.
HBMAL1 expression showed variability, peaking during different times depending on the sleep/wake condition.

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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.

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Expression of Clock Genes in Human Peripheral Blood Mononuclear Cells throughout the Sleep/Wake and Circadian Cycles

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