Cell-specific effects of acute sleep deprivation on transcriptomic signatures of non-neuronal cells in the mouse hippocampus and prefrontal cortex

Sleep is essential for maintaining cognitive, emotional, metabolic, and immune functions in animals. Although much research on sleep homeostasis has focused on neurons, non-neuronal cells are also critical. We performed transcriptomic analyses on nuclei isolated from non-neuronal cells in the hippocampus and prefrontal cortex of mice subjected to acute sleep deprivation (SD). We demonstrate that acute SD elicits robust, cell-type and region-specific transcriptional reprogramming in astrocytes and oligodrocytes. The most striking changes are in astrocyes, with reductions in cholesterol biosynthesis genes across both regions, but opposite changes in genes regulating mitochodrial and neurodegeneration-related pathways. Strikingly, we see the induction of genes associated with primary cilia in cortical astrocytes. Within oligodendrocytes, genes encoding cell-adhesion molecules are down regulated. This work highlights the importance of focusing our gene expression studies on specific cell populations and reveals new potential mechanisms for the regulation of sleep and sleep function by non-neuronal cells.