Short Report: A Meta-Analysis of the Effects of Sleep Deprivation on the Cortical Transcriptome in Animal Models

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 the present report, we used a meta-analysis of public transcriptional profiling data to discover effects of SD 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 Gemma, a database containing >19,000 re-analyzed microarray and RNA-Seq datasets. Eight studies met our systematic inclusion/exclusion criteria, characterizing the effect of 18 SD interventions on gene expression in the mouse cerebral cortex (collective n=293). For each gene with sufficient data (n=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<0.05), 104 of which were upregulated and 78 downregulated. Gene-set enrichment analysis (fGSEA) revealed down-regulation in pathways related to stress response (e.g., glucocorticoid receptor, Nr3c1), cell death and neural cell differentiation, and upregulation related to hypoxia and inflammation. Exploratory analyses found that SD duration (ranging from 3-12 hrs) did not significantly influence differential expression. However, recovery sleep (RS: 2-18 hrs) was included in three studies, and reversed the impact of SD on four transcripts. Our meta-analysis illustrates the diverse molecular impact of SD on the rodent cerebral cortex, producing effects that occasionally parallel those seen in the periphery.