TNF-α and temporal changes in sleep architecture in mice exposed to sleep fragmentation.

TNF-α plays critical roles in host-defense, sleep-wake regulation, and the pathogenesis of various disorders. Increases in the concentration of circulating TNF-α after either sleep deprivation or sleep fragmentation (SF) appear to underlie excessive daytime sleepiness in patients with sleep apnea (OSA). Following baseline recordings, mice were subjected to 15 days of SF (daily for 12 h/day from 07.00 h to 19.00 h), and sleep parameters were recorded on days1, 7 and 15. Sleep architecture and sleep propensity were assessed in both C57BL/6J and in TNF-α double receptor KO mice (TNFR KO). To further confirm the role of TNF-α, we also assessed the effect of treatment with a TNF- α neutralizing antibody in C57BL/6J mice. SF was not associated with major changes in global sleep architecture in C57BL/6J and TNFR KO mice. TNFR KO mice showed higher baseline SWS delta power. Further, following 15 days of SF, mice injected with TNF-α neutralizing antibody and TNFR KO mice showed increased EEG SWS activity. However, SWS latency, indicative of increased propensity to sleep, was only decreased in C57BL/6J, and was unaffected in TNFR KO mice as well as in C57BL/6J mice exposed to SF but treated with TNF-α neutralizing antibody. Taken together, our findings show that the excessive sleepiness incurred by recurrent arousals during sleep may be due to activation of TNF-alpha-dependent inflammatory pathways, despite the presence of preserved sleep duration and global sleep architecture.

肿瘤坏死因子 -α（TNF -α）在宿主防御、睡眠 - 觉醒调节以及多种疾病的发病机制中起着关键作用。睡眠剥夺或睡眠碎片化（SF）后循环中TNF -α浓度的升高似乎是睡眠呼吸暂停（OSA）患者白天过度嗜睡的原因。在进行基线记录之后，小鼠接受15天的睡眠碎片化处理（每天从07：00到19：00，持续12小时），并在第1、7和15天记录睡眠参数。在C57BL / 6J小鼠和TNF -α双受体敲除小鼠（TNFR KO）中评估睡眠结构和睡眠倾向。为了进一步证实TNF -α的作用，我们还评估了TNF -α中和抗体对C57BL / 6J小鼠的治疗效果。在C57BL / 6J和TNFR KO小鼠中，睡眠碎片化与整体睡眠结构的重大变化无关。TNFR KO小鼠显示出较高的基线慢波睡眠（SWS）δ功率。此外，在15天的睡眠碎片化之后，注射TNF -α中和抗体的小鼠和TNFR KO小鼠显示出脑电图慢波睡眠活动增加。然而，表明睡眠倾向增加的慢波睡眠潜伏期仅在C57BL / 6J小鼠中缩短，在TNFR KO小鼠以及接受睡眠碎片化但用TNF -α中和抗体治疗的C57BL / 6J小鼠中未受影响。综上所述，我们的研究结果表明，尽管睡眠持续时间和整体睡眠结构保持不变，但睡眠期间反复觉醒导致的过度嗜睡可能是由于TNF -α依赖性炎症通路的激活。