1] Department of Psychiatry, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, USA [2] Neuroscience Training Program, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, USA.
Neuropsychopharmacology. 2013 Dec;38(13):2578-87. doi: 10.1038/npp.2013.174. Epub 2013 Jul 18.
Epidemiological studies have shown a link between sleep loss and the obesity 'epidemic,' and several observations indicate that sleep curtailment engenders positive energy balance via increased palatable-food 'snacking.' These effects suggest alterations in reward-modulatory brain systems. We explored the effects of 10 days of sleep deprivation in rats on the expression of striatal opioid peptide (OP) genes that subserve food motivation and hedonic reward, and compared effects with those seen in hypothalamic energy balance-regulatory systems. Sleep-deprived (Sleep-Dep) rats were compared with yoked forced-locomotion apparatus controls (App-Controls), food-restricted rats (Food-Restrict), and unmanipulated controls (Home-Cage). Detection of mRNA levels with in situ hybridization revealed a subregion-specific upregulation of striatal preproenkephalin and prodynorhin gene expression in the Sleep-Dep group relative to all other groups. Neuropeptide Y (NPY) gene expression in the hippocampal dentate gyrus and throughout neocortex was also robustly upregulated selectively in the Sleep-Dep group. In contrast, parallel gene expression changes were observed in the Sleep-Dep and Food-Restrict groups in hypothalamic energy-sensing systems (arcuate nucleus NPY was upregulated, and cocaine- and amphetamine-regulated transcript was downregulated), in alignment with leptin suppression in both groups. Together, these results reveal a novel set of sleep deprivation-induced transcriptional changes in reward-modulatory peptide systems, which are dissociable from the energy-balance perturbations of sleep loss or the potentially stressful effects of the forced-locomotion procedure. The recruitment of telencephalic food-reward systems may provide a feeding drive highly resistant to feedback control, which could engender obesity through the enhancement of palatable feeding.
流行病学研究表明睡眠不足与肥胖“流行”之间存在关联，并且有几项观察结果表明，睡眠限制会通过增加美味食物“零食”摄入来产生正的能量平衡。这些影响表明奖励调节大脑系统发生了变化。我们探讨了剥夺大鼠 10 天睡眠对参与食物动机和享乐性奖励的纹状体阿片肽 (OP) 基因表达的影响，并将这些影响与下丘脑能量平衡调节系统中的影响进行了比较。与束缚于强制运动仪器的对照组 (App-Controls)、限制食物的大鼠 (Food-Restrict) 和未经处理的对照组 (Home-Cage) 相比，对睡眠剥夺的大鼠 (Sleep-Dep) 进行了比较。通过原位杂交检测 mRNA 水平显示，与其他所有组相比，睡眠剥夺组纹状体前强啡肽和前原啡肽基因表达出现亚区特异性上调。在睡眠剥夺组中，海马齿状回和整个新皮质中的神经肽 Y (NPY) 基因表达也被选择性地强烈上调。相比之下，在睡眠剥夺和限制食物的组中观察到平行的基因表达变化，在能量感应系统中（弓状核 NPY 上调，可卡因和安非他命调节转录物下调），与两组中瘦素的抑制一致。总的来说，这些结果揭示了一组新的与睡眠剥夺相关的奖励调节肽系统的转录变化，这些变化与睡眠不足的能量平衡干扰或强制运动程序的潜在压力影响是分离的。端脑食物奖励系统的募集可能提供了一种对反馈控制具有高度抵抗力的进食驱动力，这可能通过增强美味食物的摄入而导致肥胖。
