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Stress response genes protect against lethal effects of sleep deprivation in Drosophila

Nature volume 417, pages 287–291 (2002)Cite this article

Abstract

Sleep is controlled by two processes: a homeostatic drive that increases during waking and dissipates during sleep, and a circadian pacemaker that controls its timing1. Although these two systems can operate independently2,3, recent studies indicate a more intimate relationship4,5. To study the interaction between homeostatic and circadian processes in Drosophila, we examined homeostasis in the canonical loss-of-function clock mutants period (per01), timeless (tim01), clock (Clkjrk) and cycle (cyc01)6,7,8,9. cyc01 mutants showed a disproportionately large sleep rebound and died after 10 hours of sleep deprivation, although they were more resistant than other clock mutants to various stressors. Unlike other clock mutants, cyc01 flies showed a reduced expression of heat-shock genes after sleep loss. However, activating heat-shock genes before sleep deprivation rescued cyc01 flies from its lethal effects. Consistent with the protective effect of heat-shock genes, was the observation that flies carrying a mutation for the heat-shock protein Hsp83 (Hsp8308445)10 showed exaggerated homeostatic response and died after sleep deprivation. These data represent the first step in identifying the molecular mechanisms that constitute the sleep homeostat.

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Figure 1: Sleep homeostasis is altered in circadian mutants and is markedly increased in cyc01 flies.
Figure 2: cyc01 flies are resistant to stress.
Figure 3: Expression of heat-shock genes is reduced in cyc01 flies after 3 h of sleep deprivation.
Figure 4: Heat protects cyc01 flies from the lethal effects of sleep deprivation.

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Acknowledgements

We thank H. Dierick, R. Andretic and K. Long for helpful comments on the manuscript, and J. Hendricks for sharing data before publication. This work was performed at The Neurosciences Institute, which is supported by the Neurosciences Research Foundation.

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  1. Giulio Tononi

    Present address: Department of Psychiatry, University of Wisconsin-Madison, 6001 Research Park Boulevard, Madison, Wisconsin, 53711, USA

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  1. The Neurosciences Institute, 10640 John J. Hopkins Drive, San Diego, California, 92121, USA

    Paul J. Shaw, Giulio Tononi, Ralph J. Greenspan & Donald F. Robinson

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Shaw, P., Tononi, G., Greenspan, R. et al. Stress response genes protect against lethal effects of sleep deprivation in Drosophila. Nature 417, 287–291 (2002). https://doi.org/10.1038/417287a

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