Sustained Sleep Fragmentation Induces Sleep Homeostasis in Mice
Sustained Sleep Fragmentation Induces Sleep Homeostasis in Mice
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DOI：
10.5665/sleep.4572
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发表时间：
2015-04-01
期刊：
影响因子：
5.6
通讯作者：
Petit, Jean-Marie
中科院分区：
文献类型：
--
作者：
Baud, Maxime O.;Magistretti, Pierre J.;Petit, Jean-Marie
研究目的：睡眠碎片化（SF）是睡眠呼吸暂停和其他常见睡眠障碍的一个重要特征。尽管反复唤醒对认知表现的影响已有文献记载，但长期睡眠睡眠对脑电图（EEG）和睡眠稳态分子标记的影响仍未得到充分研究。为了解决这个问题，我们建立了慢性SF小鼠模型，并表征了其对脑电图频谱频率的影响以及先前与睡眠稳态相关的基因表达，包括时钟基因、热休克蛋白和可塑性相关基因。设计:N / A。单位：动物睡眠研究实验室。实验对象：C57BL6/J成年小鼠66只。干预措施：在14天内以60/h的速率进行工具性睡眠中断。测量和结果：在SF 14天期间记录运动活动和脑电图，随后恢复2天。尽管唤醒次数和睡眠持续时间显著减少，但SF最低限度地减少了睡眠总量，并没有显著改变其昼夜节律分布。SF期间的频谱分析显示慢波活动（SWA; 1-4 Hz）和其他频率（4-40 Hz）具有稳态驱动。恢复期间的记录显示慢波睡眠巩固和短暂的SWA反弹，以及矛盾的睡眠持续时间。慢性SF不诱导所选基因的表达。结论：慢性睡眠片段化（SF）增加了睡眠压力，证实了质量的改变和数量的保留触发了核心睡眠稳态机制。然而，它没有诱导睡眠缺失诱导的基因表达，提示这些分子通路在涉及SF的慢性疾病中不能持续激活。
Study Objectives: Sleep fragmentation (SF) is an integral feature of sleep apnea and other prevalent sleep disorders. Although the effect of repetitive arousals on cognitive performance is well documented, the effects of long-term SF on electroencephalography (EEG) and molecular markers of sleep homeostasis remain poorly investigated. To address this question, we developed a mouse model of chronic SF and characterized its effect on EEG spectral frequencies and the expression of genes previously linked to sleep homeostasis including clock genes, heat shock proteins, and plasticity-related genes.Design: N/A.Setting: Animal sleep research laboratory.Participants : Sixty-six C57BL6/J adult mice.Interventions: Instrumental sleep disruption at a rate of 60/h during 14 daysMeasurements and Results: Locomotor activity and EEG were recorded during 14 days of SF followed by recovery for 2 days. Despite a dramatic number of arousals and decreased sleep bout duration, SF minimally reduced total quantity of sleep and did not significantly alter its circadian distribution. Spectral analysis during SF revealed a homeostatic drive for slow wave activity (SWA; 1-4 Hz) and other frequencies as well (4-40 Hz). Recordings during recovery revealed slow wave sleep consolidation and a transient rebound in SWA, and paradoxical sleep duration. The expression of selected genes was not induced following chronic SF.Conclusions: Chronic sleep fragmentation (SF) increased sleep pressure confirming that altered quality with preserved quantity triggers core sleep homeostasis mechanisms. However, it did not induce the expression of genes induced by sleep loss, suggesting that these molecular pathways are not sustainably activated in chronic diseases involving SF.