Functional Polymorphisms in Dopaminergic Genes Modulate Neurobehavioral and Neurophysiological Consequences of Sleep Deprivation.
Functional Polymorphisms in Dopaminergic Genes Modulate Neurobehavioral and Neurophysiological Consequences of Sleep Deprivation.
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DOI：
10.1038/srep45982
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发表时间：
2017-04-10
影响因子：
4.6
通讯作者：
Landolt HP
中科院分区：
文献类型：
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作者：
Holst SC;Müller T;Valomon A;Seebauer B;Berger W;Landolt HP
睡眠不足会损害认知能力，并且会改变清醒和睡眠时的大脑活动。然而，长时间清醒的分子调节机制仍然知之甚少。来自遗传学、行为学、药理学和影像学研究的证据表明，多巴胺能信号有助于睡眠缺失的行为和脑电图（EEG）后果，尽管缺乏直接的人类证据。我们测试了多巴胺神经传递是否调节长时间清醒时的持续注意和脑电图功率的演变。在这里，我们研究了多巴胺转运蛋白（DAT1）和多巴胺D2受体（DRD2）基因的功能性遗传变异对64至82名健康志愿者在40小时清醒状态下精神运动表现和标准化清醒脑电图振荡的影响。睡眠剥夺持续增强了睡意、注意力缺失和醒着时脑电图的能量比（TAR）。重要的是，DAT1和DRD2基因型明显调节睡眠缺失引起的主观嗜睡、PVT缺失和TAR的变化，呈倒u型关系。总之，这些数据表明，基因决定的DAT1和DRD2表达差异调节睡眠剥夺的功能后果，支持纹状体-丘脑-皮质多巴胺能通路调节人类睡眠缺失的神经行为和神经生理后果的假设。
Sleep deprivation impairs cognitive performance and reliably alters brain activation in wakefulness and sleep. Nevertheless, the molecular regulators of prolonged wakefulness remain poorly understood. Evidence from genetic, behavioral, pharmacologic and imaging studies suggest that dopaminergic signaling contributes to the behavioral and electroencephalographic (EEG) consequences of sleep loss, although direct human evidence thereof is missing. We tested whether dopamine neurotransmission regulate sustained attention and evolution of EEG power during prolonged wakefulness. Here, we studied the effects of functional genetic variation in the dopamine transporter (DAT1) and the dopamine D2 receptor (DRD2) genes, on psychomotor performance and standardized waking EEG oscillations during 40 hours of wakefulness in 64 to 82 healthy volunteers. Sleep deprivation consistently enhanced sleepiness, lapses of attention and the theta-to-alpha power ratio (TAR) in the waking EEG. Importantly, DAT1 and DRD2 genotypes distinctly modulated sleep loss-induced changes in subjective sleepiness, PVT lapses and TAR, according to inverted U-shaped relationships. Together, the data suggest that genetically determined differences in DAT1 and DRD2 expression modulate functional consequences of sleep deprivation, supporting the hypothesis that striato-thalamo-cortical dopaminergic pathways modulate the neurobehavioral and neurophysiological consequences of sleep loss in humans.