Rhoads Cosette A, Hagenauer Megan H, Xiong Jinglin, Hernandez Erin, Nguyen Duy Manh, Saffron Annaka, Flandreau Elizabeth, Watson Stanley, Akil Huda
Grinnell College, Grinnell, IA USA.
Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI USA.
bioRxiv. 2025 Aug 2:2025.04.21.648791. doi: 10.1101/2025.04.21.648791.
Sleep deprivation (SD) causes large disturbances in mood and cognition. The molecular basis for these effects can be explored using transcriptional profiling to quantify brain gene expression. In this report, we used a meta-analysis of public transcriptional profiling data to discover SD effects on gene expression that are consistent across studies and paradigms. To conduct the meta-analysis, we used pre-specified search terms related to rodent SD paradigms to identify relevant studies within , a database containing >19,000 re-analyzed microarray and RNA-Seq datasets. Eight studies met our systematic inclusion/exclusion criteria. These studies characterized the effect of 18 SD interventions on gene expression in the mouse cerebral cortex (collective =293). For each gene with sufficient data (=16,290), we fit a random effects meta-analysis model to the SD effect sizes (log(2) fold changes). Our meta-analysis revealed 182 differentially expressed genes in response to SD (false discovery rate: FDR<0.05), most of which (115/182) showed similar effects (FDR<0.05) in an independent large dataset (: =86 RNA-Seq samples from =222 mice). Gene-set enrichment analysis revealed down-regulation in pathways related to stress response (e.g., glucocorticoid receptor ), vasculature, growth and development, and upregulation related to stress, inflammation, and neuropeptide signalling. Exploratory analyses suggested that recovery sleep (included in six contrasts: range: 1-18 hrs), could reverse the impact of SD on gene expression. Our meta-analysis provides a useful reference database illustrating the diverse molecular impact of SD on the rodent cerebral cortex.
睡眠剥夺（SD）会导致情绪和认知出现严重紊乱。可以通过转录谱分析来量化大脑基因表达，从而探究这些影响的分子基础。在本报告中，我们对公开的转录谱数据进行了荟萃分析，以发现跨研究和范式一致的睡眠剥夺对基因表达的影响。为了进行荟萃分析，我们使用了与啮齿动物睡眠剥夺范式相关的预先指定的搜索词，在一个包含超过19,000个重新分析的微阵列和RNA测序数据集的数据库中识别相关研究。八项研究符合我们的系统纳入/排除标准。这些研究描述了18种睡眠剥夺干预对小鼠大脑皮层基因表达的影响（总计 = 293）。对于每个有足够数据的基因（= 16,290），我们对睡眠剥夺效应大小（log(2)倍数变化）拟合了随机效应荟萃分析模型。我们的荟萃分析揭示了182个因睡眠剥夺而差异表达的基因（错误发现率：FDR < 0.05），其中大多数（115/182）在一个独立的大型数据集中显示出相似的效应（FDR < 0.05）（： = 来自222只小鼠的86个RNA测序样本）。基因集富集分析显示，与应激反应（如糖皮质激素受体）、脉管系统、生长和发育相关的途径下调，与应激、炎症和神经肽信号传导相关的途径上调。探索性分析表明，恢复睡眠（包含在六个对比中：范围：1 - 18小时）可以逆转睡眠剥夺对基因表达的影响。我们的荟萃分析提供了一个有用的参考数据库，说明了睡眠剥夺对啮齿动物大脑皮层的多种分子影响。
