Stenvers Dirk Jan, van Dorp Rick, Foppen Ewout, Mendoza Jorge, Opperhuizen Anne-Loes, Fliers Eric, Bisschop Peter H, Meijer Johanna H, Kalsbeek Andries, Deboer Tom
Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.
Institute of Cellular and Integrative Neurosciences, CNRS UPR3212, University of Strasbourg, France.
Sci Rep. 2016 Oct 20;6:35662. doi: 10.1038/srep35662.
Exposure to light at night (LAN) is associated with insomnia in humans. Light provides the main input to the master clock in the hypothalamic suprachiasmatic nucleus (SCN) that coordinates the sleep-wake cycle. We aimed to develop a rodent model for the effects of LAN on sleep. Therefore, we exposed male Wistar rats to either a 12 h light (150-200lux):12 h dark (LD) schedule or a 12 h light (150-200 lux):12 h dim white light (5 lux) (LDim) schedule. LDim acutely decreased the amplitude of daily rhythms of REM and NREM sleep, with a further decrease over the following days. LDim diminished the rhythms of 1) the circadian 16-19 Hz frequency domain within the NREM sleep EEG, and 2) SCN clock gene expression. LDim also induced internal desynchronization in locomotor activity by introducing a free running rhythm with a period of ~25 h next to the entrained 24 h rhythm. LDim did not affect body weight or glucose tolerance. In conclusion, we introduce the first rodent model for disturbed circadian control of sleep due to LAN. We show that internal desynchronization is possible in a 24 h L:D cycle which suggests that a similar desynchronization may explain the association between LAN and human insomnia.
夜间光照（LAN）与人类失眠有关。光线为下丘脑视交叉上核（SCN）中的主时钟提供主要输入，该主时钟协调睡眠-觉醒周期。我们旨在建立一种用于研究LAN对睡眠影响的啮齿动物模型。因此，我们将雄性Wistar大鼠暴露于12小时光照（150 - 200勒克斯）：12小时黑暗（LD）的时间表或12小时光照（150 - 200勒克斯）：12小时昏暗白光（5勒克斯）（LDim）的时间表下。LDim急性降低了快速眼动（REM）和非快速眼动（NREM）睡眠的每日节律幅度，在接下来的几天中进一步降低。LDim减弱了以下两种节律：1）NREM睡眠脑电图中昼夜节律的16 - 19赫兹频域；2）SCN时钟基因表达。LDim还通过在夹带的24小时节律旁边引入一个周期约为25小时的自由运行节律，诱导了运动活动的内部去同步化。LDim不影响体重或葡萄糖耐量。总之，我们引入了第一个由于LAN导致昼夜节律性睡眠控制紊乱的啮齿动物模型。我们表明在24小时的明暗周期中可能会出现内部去同步化，这表明类似的去同步化可能解释了LAN与人类失眠之间的关联。
