Arnardottir Erna S, Nikonova Elena V, Shockley Keith R, Podtelezhnikov Alexei A, Anafi Ron C, Tanis Keith Q, Maislin Greg, Stone David J, Renger John J, Winrow Christopher J, Pack Allan I
Center for Sleep and Circadian Neurobiology and Division of Sleep Medicine/Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA and Department of Respiratory Medicine and Sleep, Landspitali - The National University Hospital, Iceland and Faculty of Medicine, University of Iceland, Iceland.
Department of Exploratory and Translational Sciences, Merck Research Laboratories, West Point, PA.
Sleep. 2014 Oct 1;37(10):1589-600. doi: 10.5665/sleep.4064.
To address whether changes in gene expression in blood cells with sleep loss are different in individuals resistant and sensitive to sleep deprivation.
Blood draws every 4 h during a 3-day study: 24-h normal baseline, 38 h of continuous wakefulness and subsequent recovery sleep, for a total of 19 time-points per subject, with every 2-h psychomotor vigilance task (PVT) assessment when awake.
Sleep laboratory.
Fourteen subjects who were previously identified as behaviorally resistant (n = 7) or sensitive (n = 7) to sleep deprivation by PVT.
Thirty-eight hours of continuous wakefulness.
We found 4,481 unique genes with a significant 24-h diurnal rhythm during a normal sleep-wake cycle in blood (false discovery rate [FDR] < 5%). Biological pathways were enriched for biosynthetic processes during sleep. After accounting for circadian effects, two genes (SREBF1 and CPT1A, both involved in lipid metabolism) exhibited small, but significant, linear changes in expression with the duration of sleep deprivation (FDR < 5%). The main change with sleep deprivation was a reduction in the amplitude of the diurnal rhythm of expression of normally cycling probe sets. This reduction was noticeably higher in behaviorally resistant subjects than sensitive subjects, at any given P value. Furthermore, blood cell type enrichment analysis showed that the expression pattern difference between sensitive and resistant subjects is mainly found in cells of myeloid origin, such as monocytes.
Individual differences in behavioral effects of sleep deprivation are associated with differences in diurnal amplitude of gene expression for genes that show circadian rhythmicity.
探讨睡眠不足时血细胞中基因表达的变化在对睡眠剥夺有抵抗力和敏感的个体中是否存在差异。
在一项为期3天的研究中，每4小时采集一次血液：24小时正常基线期、38小时持续清醒期以及随后的恢复睡眠期，每位受试者共19个时间点，清醒时每2小时进行一次精神运动警觉性任务（PVT）评估。
睡眠实验室。
14名先前通过PVT被确定为对睡眠剥夺行为上有抵抗力（n = 7）或敏感（n = 7）的受试者。
38小时持续清醒。
我们发现4481个独特基因在血液正常睡眠 - 觉醒周期中有显著的24小时昼夜节律（错误发现率[FDR] < 5%）。睡眠期间生物合成过程的生物途径得到富集。在考虑昼夜节律影响后，两个基因（SREBF1和CPT1A，均参与脂质代谢）的表达随睡眠剥夺持续时间呈现微小但显著的线性变化（FDR < 5%）。睡眠剥夺的主要变化是正常循环探针集表达的昼夜节律振幅降低。在任何给定的P值下，行为上有抵抗力的受试者中这种降低明显高于敏感受试者。此外，血细胞类型富集分析表明，敏感和有抵抗力的受试者之间的表达模式差异主要存在于髓系来源的细胞中，如单核细胞。
睡眠剥夺行为效应的个体差异与显示昼夜节律性的基因表达昼夜振幅差异有关。
