Cellular damage, including wounding, drives C. elegans stress-induced sleep

Abstract

Across animal phyla, sleep is associated with increased cellular repair, suggesting that cellular damage may be a core component of sleep pressure. In support of this notion, sleep in the nematode Caenorhabditis elegans can be triggered by damaging conditions, including noxious heat, high salt, and ultraviolet light exposure. It is not clear, however, whether this stress-induced sleep (SIS) is a direct consequence of cellular damage, or of a resulting energy deficit, or whether it is triggered simply by the sensation of noxious conditions. Here, we show that thermosensation is dispensable for heat-induced sleep, that osmosensation is dispensable for salt-induced sleep, and that wounding is also a sleep trigger, together indicating that SIS is not triggered by sensation of noxious environments. We present evidence that genetic variation in cellular repair pathways impacts sleep amount, and that SIS involves systemic monitoring of cellular damage. We show that the low-energy sensor AMP-activated protein kinase (AMPK) is not required for SIS, suggesting that energy deficit is not the primary sleep trigger. Instead, AMPK-deficient animals display enhanced SIS responses, and pharmacological activation of AMPK reduces SIS, suggesting that ATP-dependent repair of cellular damage mitigates sleep pressure.

Keywords:

• Sleep
• SIS
• proteotoxic stress
• genotoxic stress
• wounding
• AMPK

Acknowledgements

The authors thank the Caenorhabditis Genetics Center (CGC) and Ikue Mori for strains. Special thanks to Alex Hernandez of BIOL447/L for observing that wounding could trigger ALA-dependent sleep. This article is dedicated to Sydney Brenner.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by an NSF–CAREER award [IOS 1553673] to CVB. The Caenorhabditis Genetics Center is funded by the NIH Office of Research Infrastructure Programs [P40 OD010440].