Plasma and CSF Proteomic Signatures of Acutely Sleep-Deprived Humans: An Exploratory Study

Ana Vaquer-Alicea, Jinsheng Yu, Haiyan Liu, Brendan P Lucey
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Abstract

Abstract Study objectives Acute sleep deprivation affects both central and peripheral biological processes. Prior research has mainly focused on specific proteins or biological pathways that are dysregulated in the setting of sustained wakefulness. This exploratory study aimed to provide a comprehensive view of the biological processes and proteins impacted by acute sleep deprivation in both plasma and cerebrospinal fluid (CSF). Methods We collected plasma and CSF from human participants during one night of sleep deprivation and control normal sleep conditions. 1300 proteins were measured at hour 0 and hour 24 using a high-scale aptamer-based proteomics platform (SOMAscan) and a systematic biological database tool (Metascape) was used to reveal altered biological pathways. Results Acute sleep deprivation decreased the number of upregulated and downregulated biological pathways and proteins in plasma but increased upregulated and downregulated biological pathways and proteins in CSF. Predominantly affected proteins and pathways were associated with immune response, inflammation, phosphorylation, membrane signaling, cell-cell adhesion, and extracellular matrix organization. Conclusions The identified modifications across biofluids adds to evidence that acute sleep deprivation has important impacts on biological pathways and proteins that can negatively affect human health. As a hypothesis-driving study, these findings may help with the exploration of novel mechanisms that mediate sleep loss and associated conditions, drive the discovery of new sleep loss biomarkers, and ultimately aid in the identification of new targets for intervention to human diseases.
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急性睡眠剥夺人类血浆和脑脊液蛋白质组学特征:一项探索性研究
研究目的急性睡眠剥夺影响中枢和外周生物过程。先前的研究主要集中在持续清醒状态下失调的特定蛋白质或生物途径上。本探索性研究旨在全面了解急性睡眠剥夺对血浆和脑脊液(CSF)的生物学过程和蛋白质的影响。方法在睡眠剥夺1晚期间采集受试者血浆和脑脊液,并控制正常睡眠条件。使用基于适配体的大规模蛋白质组学平台(SOMAscan)和系统生物数据库工具(metscape)在第0小时和第24小时测量1300个蛋白质,以揭示改变的生物途径。结果急性睡眠剥夺使血浆中上调和下调的生物通路和蛋白数量减少,而脑脊液中上调和下调的生物通路和蛋白数量增加。主要受影响的蛋白质和途径与免疫反应、炎症、磷酸化、膜信号传导、细胞-细胞粘附和细胞外基质组织有关。在生物体液中发现的变化进一步证明,急性睡眠剥夺对生物通路和蛋白质有重要影响,可能对人类健康产生负面影响。作为一项假设驱动的研究,这些发现可能有助于探索介导睡眠不足和相关疾病的新机制,推动发现新的睡眠不足生物标志物,并最终有助于确定干预人类疾病的新靶点。
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