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绝非微不足道:微觉醒处于去甲肾上腺素信号传导与关键睡眠功能的交叉点上。

Anything but small: Microarousals stand at the crossroad between noradrenaline signaling and key sleep functions.

作者信息

Lüthi Anita, Nedergaard Maiken

机构信息

Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.

Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, University of Copenhagen, Copenhagen, Denmark; Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY, USA.

出版信息

Neuron. 2025 Feb 19;113(4):509-523. doi: 10.1016/j.neuron.2024.12.009. Epub 2025 Jan 13.

Abstract

Continuous sleep restores the brain and body, whereas fragmented sleep harms cognition and health. Microarousals (MAs), brief (3- to 15-s-long) wake intrusions into sleep, are clinical markers for various sleep disorders. Recent rodent studies show that MAs during healthy non-rapid eye movement (NREM) sleep are driven by infraslow fluctuations of noradrenaline (NA) in coordination with electrophysiological rhythms, vasomotor activity, cerebral blood volume, and glymphatic flow. MAs are hence part of healthy sleep dynamics, raising questions about their biological roles. We propose that MAs bolster NREM sleep's benefits associated with NA fluctuations, according to an inverted U-shaped curve. Weakened noradrenergic fluctuations, as may occur in neurodegenerative diseases or with sleep aids, reduce MAs, whereas exacerbated fluctuations caused by stress fragment NREM sleep and collapse NA signaling. We suggest that MAs are crucial for the restorative and plasticity-promoting functions of sleep and advance our insight into normal and pathological arousal dynamics from sleep.

摘要

持续睡眠可恢复大脑和身体机能,而碎片化睡眠则会损害认知和健康。微觉醒(MAs)是指短暂(3至15秒长)的清醒状态侵入睡眠,是各种睡眠障碍的临床指标。最近的啮齿动物研究表明,健康的非快速眼动(NREM)睡眠期间的微觉醒是由去甲肾上腺素(NA)的超慢波动与电生理节律、血管运动活动、脑血容量和类淋巴液流动协同驱动的。因此,微觉醒是健康睡眠动态的一部分,这引发了人们对其生物学作用的质疑。我们提出,根据倒U形曲线,微觉醒增强了与NA波动相关的NREM睡眠的益处。去甲肾上腺素能波动减弱,如在神经退行性疾病中或使用助眠药物时可能发生的情况,会减少微觉醒,而由压力引起的波动加剧则会使NREM睡眠碎片化并破坏NA信号传导。我们认为微觉醒对于睡眠的恢复和促进可塑性的功能至关重要,并增进了我们对正常和病理性睡眠觉醒动态的理解。

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