Cross-translational studies in human and Drosophila identify markers of sleep loss.
Cross-translational studies in human and Drosophila identify markers of sleep loss.
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DOI：
10.1371/journal.pone.0061016
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Shaw PJ
中科院分区：
文献类型：
--
作者：
Thimgan MS;Gottschalk L;Toedebusch C;McLeland J;Rechtschaffen A;Gilliland-Roberts M;Duntley SP;Shaw PJ
睡眠不足已经成为一种流行病，这给公共健康和安全带来了巨大的负担。目前，还没有客观的测试来确定一个人是否长时间没有睡眠。在这里，我们描述了一种新的方法，利用睡眠的进化保守性来识别睡眠不足的标志物。开始，我们证明，IL-6增加大鼠慢性完全睡眠剥夺和人类清醒后30小时。然后对从睡眠剥夺的人类受试者中提取的唾液进行发现实验，以确定候选标记。鉴于睡眠与免疫力之间的关系，我们使用人类炎症低密度阵列来筛选唾液中的睡眠剥夺新标志物。在睡眠丧失30 h后，整合素αM（ITGAM）和Anaxin A3（AnxA 3）显著升高。为了证实这些结果，我们使用QPCR来评估清醒24小时后收集的独立样本中的ITGAM和AnxA 3;这两种转录本都增加了。然后使用果蝇遗传学的力量作为成本效益的手段来进一步评估这些标记的行为，以确定标记是否与睡眠缺失或其他混淆因素（例如，应力）。果蝇的转录谱表明，ITGAM的果蝇同源物不能预测睡眠丧失。因此，我们研究了果蝇中整合素家族其他成员的转录水平。只有Scab（整合素α5（ITGA 5）的果蝇同源物）的转录水平与长时间清醒的脆弱性相关。由于ITGA 5不包括在低密度阵列中，我们回到人类样本，发现ITGA 5转录水平在睡眠剥夺后增加。这些交叉翻译数据表明，苍蝇和人类的发现实验是相互加强的，可以互换使用，以确定候选的睡眠丧失的生物标志物。
Inadequate sleep has become endemic, which imposes a substantial burden for public health and safety. At present, there are no objective tests to determine if an individual has gone without sleep for an extended period of time. Here we describe a novel approach that takes advantage of the evolutionary conservation of sleep to identify markers of sleep loss. To begin, we demonstrate that IL-6 is increased in rats following chronic total sleep deprivation and in humans following 30 h of waking. Discovery experiments were then conducted on saliva taken from sleep-deprived human subjects to identify candidate markers. Given the relationship between sleep and immunity, we used Human Inflammation Low Density Arrays to screen saliva for novel markers of sleep deprivation. Integrin αM (ITGAM) and Anaxin A3 (AnxA3) were significantly elevated following 30 h of sleep loss. To confirm these results, we used QPCR to evaluate ITGAM and AnxA3 in independent samples collected after 24 h of waking; both transcripts were increased. The behavior of these markers was then evaluated further using the power of Drosophila genetics as a cost-effective means to determine whether the marker is associated with vulnerability to sleep loss or other confounding factors (e.g., stress). Transcript profiling in flies indicated that the Drosophila homologues of ITGAM were not predictive of sleep loss. Thus, we examined transcript levels of additional members of the integrin family in flies. Only transcript levels of scab, the Drosophila homologue of Integrin α5 (ITGA5), were associated with vulnerability to extended waking. Since ITGA5 was not included on the Low Density Array, we returned to human samples and found that ITGA5 transcript levels were increased following sleep deprivation. These cross-translational data indicate that fly and human discovery experiments are mutually reinforcing and can be used interchangeably to identify candidate biomarkers of sleep loss.
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影响因子：
11
作者：
Allebrandt, K. V.;Amin, N.;Roenneberg, T.
通讯作者：
Roenneberg, T.
影响因子：
15.1
作者：
Burgos, I;Richter, L;Riemann, D
通讯作者：
Riemann, D
影响因子：
5.6
作者：
Haack, Monika;Sanchez, Elsa;Mullington, Janet M.
通讯作者：
Mullington, Janet M.
DOI：
10.3758/bf03200977
发表时间：
1985-12-01
期刊：
BEHAVIOR RESEARCH METHODS INSTRUMENTS & COMPUTERS
影响因子：
--
作者：
DINGES, DF;POWELL, JW
通讯作者：
POWELL, JW
影响因子：
5.6
作者：
EVERSON, CA;BERGMANN, BM;RECHTSCHAFFEN, A
通讯作者：
RECHTSCHAFFEN, A