The peripheral genome-wide gene expression profiles in humans after prolonged wakefulness and sleep recovery

Although the specific functions of sleep have not been completely elucidated, the literature has suggested that sleep is essential for proper homeostasis. Sleep loss is associated with changes in behavioral, neurochemical, cellular, and metabolic function as well as impaired immune response. We evaluated the gene expression profiles of healthy male volunteers who underwent 60 hours of prolonged wakefulness (PW) followed by 12 hours of sleep recovery (SR) using high-resolution microarrays. Peripheral whole blood was collected at 8 am in the morning before the initiation of PW (baseline), after the second night of PW, and one night after SR. We identified over 500 genes that were differentially expressed. Notably, these genes were related to DNA damage and repair and stress response as well diverse immune system responses such as natural killer pathways including killer cell lectin-like receptors family, as well granzymes and T-cell receptors which play important roles in host defense. These results support the idea that sleep loss can lead to alterations in molecular processes that result in perturbation of cellular immunity, induction of inflammatory responses, and homeostatic imbalance. Moreover, expression of multiple genes was down-regulated following PW and up-regulated after SR compared to PW, suggesting an attempt of the body to re-establish internal homeostasis. In silico validation of alterations in the expression of CETN3, DNAJC and CEACAM genes, confirmed previous findings related to the molecular effects of sleep deprivation. Thus, the present findings confirm that the effects of sleep loss are not restricted to the brain and can occur intensely in peripheral tissues.

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Pellegrino R, Sunaga DY, Guindalini C, Martins RC, Mazzotti DR, Wei Z, Daye ZJ, Andersen ML, Tufik S