Lactate as a Biomarker for Sleep

Lactate as a Biomarker for Sleep
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DOI:
10.5665/sleep.2072
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发表时间:
2012-09-01
期刊:
影响因子:
5.6
通讯作者:
Petillo, Peter A.
Petillo, Peter A.
中科院分区:
医学2区
文献类型:
--
作者:
Naylor, Erik;Aillon, Daniel V.;Petillo, Peter A.

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研究目标:理想的睡眠生物标志物应随着睡眠开始而迅速变化,在整个睡眠期间保持在可检测的差异水平,并在醒来时表现出快速变化。目前,尚未发现具有所有这三种特性的分子标记。本研究检查了三种物质(乳酸、葡萄糖和谷氨酸)作为睡眠生物标志物的适用性。设计:使用电流生物传感器技术结合脑电图 (EEG) 和肌电图 (EMG) 监测,在多个睡眠/觉醒周期记录乳酸和葡萄糖(队列 1)以及乳酸和谷氨酸(队列 2)的细胞外浓度。患者或参与者:有 12 名患者C57Bl/6J 雄性小鼠(3-5 个月大)。干预:使用脑电图记录识别睡眠和清醒的转变。在过渡事件之前和期间以及延长睡眠期间和 6 小时睡眠剥夺期间评估细胞外乳酸、葡萄糖和谷氨酸浓度。测量和结果:在醒来和快速眼动睡眠期间立即观察到皮质乳酸浓度快速且持续增加(约 15 μM/min)。在连续醒来的 6 小时期间,乳酸浓度也保持升高。在非快速动眼睡眠期间测量到乳酸浓度持续下降。谷氨酸盐表现出类似的模式,但上升和下降速度慢得多(约 0.03 μM/min)。葡萄糖浓度变化并未表现出与睡眠或觉醒之间的明显相关性。结论:这些发现表明细胞外乳酸浓度是可靠的睡眠/觉醒生物标志物,并且可以独立于脑电图信号使用。
Study Objectives: An ideal biomarker for sleep should change rapidly with sleep onset, remain at a detectably differential level throughout the sleep period, and exhibit a rapid change with waking. Currently, no molecular marker has been identified that exhibits all three properties. This study examined three substances (lactate, glucose, and glutamate) for suitability as a sleep biomarker.Design: Using amperometric biosensor technology in conjunction with electroencephalograph (EEG) and electromyograph (EMG) monitoring, extracellular concentrations of lactate and glucose (Cohort 1) as well as lactate and glutamate (Cohort 2) were recorded over multiple sleep/wake cycles.Patients or Participants: There were 12 C57Bl/6J male mice (3-5 mo old).Interventions: Sleep and waking transitions were identified using EEG recordings. Extracellular concentrations of lactate, glucose, and glutamate were evaluated before and during transition events as well as during extended sleep and during a 6-h sleep deprivation period.Measurements and Results: Rapid and sustained increases in cortical lactate concentration (approximately 15 mu M/min) were immediately observed upon waking and during rapid eye movement sleep. Elevated lactate concentration was also maintained throughout a 6-h period of continuous waking. A persistent and sustained decline in lactate concentration was measured during nonrapid eye movement sleep. Glutamate exhibited similar patterns, but with a much slower rise and decline (approximately 0.03 mu M/min). Glucose concentration changes did not demonstrate a clear correlation with either sleep or wake.Conclusions: These findings indicate that extracellular lactate concentration is a reliable sleep/wake biomarker and can be used independently of the EEG signal.