Molecular correlates of sleep deprivation in the mouse brain identified by meta-analysis of microarray data
Abdalla OHMH., Dunlop E., Wilson TS., Reardon PK., Iqbal M., Tam SKE., Vyazovskiy VV., Ray DW., Brown LA., Cheng HYM., Peirson SN.
Studying the transcriptional changes in the brain following sleep deprivation has provided insight into the molecular mechanisms that differ between sleep and wake. Individual studies are limited in their ability to detect differentially expressed genes due to small sample size. Here we performed a meta-analysis of published brain expression data, totalling 173 microarrays across 245 mice. 498 genes were identified as significantly changing with sleep-deprivation at q < 0.01, 96 of which were previously identified by the original studies. Of the remaining 402 novel candidate sleep genes, 14 were associated with human sleep traits and 3 with sleep phenotypes in knockout mice. Candidate gene validation showed significant upregulation of Rasd1 ( Dexras1 ) following sleep deprivation, and phenotyping of Rasd1 KO mice revealed changes in the amount and distribution of behavioural sleep duration and sleep bout structure. These results provide a greater understanding of the molecular correlates of sleep and provide a resource for the sleep research community.