Editors' ChoicePhysiology

Sleepless with ROS

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Science Signaling  23 Jun 2020:
Vol. 13, Issue 637, eabd4212
DOI: 10.1126/scisignal.abd4214

Sleep deprivation may kill because it induces ROS accumulation and increased oxidative stress in the gut.

Sleep deprivation is eventually fatal. To investigate why, Vaccaro et al. developed a method to ensure continual sleep deprivation in Drosophila through thermogenetic activation of neurons that suppress sleep. This approach prevented the compensatory increase in sleep drive or rebound sleep that usually occurs after sleep deprivation. Sleep-deprived flies showed an increase in reactive oxygen species (ROS) concentrations in the gut, a finding that was confirmed by other methods of sleep deprivation, such as mechanical agitation or RNA interference directed against proteins that promote sleep. The guts of sleep-deprived Drosophila as well as those of sleep-deprived mice showed signs of oxidative stress, including DNA damage, stress granule formation, and cell death. Dietary supplements that neutralized ROS in the gut or enterocyte-specific expression of the antioxidant enzymes superoxidase dismutase 1 or 2 (SOD1 or SOD2) or catalase increased the survival of sleep-deprived Drosophila. Thus, accumulation of ROS in the gut leading to oxidative stress may be a reason why sleep deprivation is deadly.

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