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Stress response genes protect against lethal effects of sleep deprivation in Drosophila
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 timing. Although these two systems can operate independently, recent studies indicate a more intimate relationship. To study the interaction between homeostatic and circadian processes in Drosophila, we examined homeostasis in the canonical loss-of-function clock mutants period (per(01)), timeless (tim(01)), clock (Clk(jrk)) and cycle (cyc(01)). cyc(01) 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, cyc(01) flies showed a reduced expression of heat-shock genes after sleep loss. However, activating heat-shock genes before sleep deprivation rescued cyc(01) 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 (Hsp83(08445)) 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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Continuous sleep deprivation kills rodents and flies within a period of days to weeks.
“continuous sleep deprivation kills rodents and flies within a period of days to weeks (5, 6).”
From Sleep Drives Metabolite Clearance from the Adult Brain (2013) · cites this paper as [6]
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Research works printed but not linked: 30
- Borbely, A. A. & Achermann, P. Sleep homeostasis and models of sleep regulation. J. Biol. Rhythms 14, 557–568 (1999)
- Mistlberger, R. E., Bergmann, B. M., Waldenar, W. & Rechtschaffen, A. Recovery sleep following sleep deprivation in intact and suprachiasmatic nuclei-lesioned rats. Sleep 6, 217–233 (1983) · DOI
- Tobler, I., Borbely, A. A. & Groos, G. The effect of sleep deprivation on sleep in rats with suprachiasmatic lesions. Neurosci. Lett. 42, 49–54 (1983) · DOI
- Naylor, E. et al. The circadian clock mutation alters sleep homeostasis in the mouse. J. Neurosci. 20, 8138–8143 (2000) · DOI · Paper page
- Antle, M. C. & Mistlberger, R. E. Circadian clock resetting by sleep deprivation without exercise in the Syrian hamster. J. Neurosci. 20, 9326–9332 (2000) · DOI
- Konopka, R. & Benzer, S. Clock mutants of Drosophila melanogaster. Proc. Natl Acad. Sci. USA 68, 2112–2116 (1971) · DOI
- Sehgal, A., Price, J. L., Man, B. & Young, M. W. Loss of circadian behavioural rhythms and per RNA oscillations in the Drosophila mutant timeless. Science 263, 1603–1606 (1994) · DOI
- Allada, R., White, N. E., So, W. V., Hall, J. C. & Rosbash, M. A mutant Drosophila homolog of mammalian Clock disrupts circadian rhythms and transcription of period and timeless. Cell 93, 791–804 (1998) · DOI
- Rutila, J. E. et al. CYCLE is a second bHLH-PAS clock protein essential for circadian rhythmicity and transcription of Drosophila period and timeless. Cell 93, 805–814 (1998) · DOI
- Castrillon, D. H. et al. Toward a molecular genetic analysis of spermatogenesis in Drosophila melanogaster: characterization of male-sterile mutants generated by single P element mutagenesis. Genetics 135, 489–505 (1993) · DOI
- Shaw, P. J., Cirelli, C., Greenspan, R. J. & Tononi, G. Correlates of sleep and waking in Drosophila melanogaster. Science 287, 1834–1837 (2000) · DOI
- Hendricks, J. C. et al. Rest in Drosophila is a sleep-like state. Neuron 25, 129–138 (2000) · DOI · Paper page
- Edgar, D. M., Dement, W. C. & Fuller, C. A. Effect of SCN lesions on sleep in squirrel monkeys: Evidence for opponent processes in sleep–wake regulation. J. Neurosci. 13, 1065–1079 (1993) · DOI
- Dijk, D. J. & Czeisler, C. A. Paradoxical timing of the circadian rhythm of sleep propensity serves to consolidate sleep and wakefulness in humans. Neurosci. Lett. 166, 63–68 (1994) · DOI · Paper page
- Homyk, T., Szidonya, J. & Suzuki, D. T. Behavioral mutants of Drosophila melanogaster. Mol. Gen. Genet. 177, 553–565 (1980) · DOI
- Armitage, R., Smith, C., Thompson, S. & Hoffman, R. Sex differences in slow-wave activity in response to sleep deprivation. Sleep Res. Online 4, 33–41 (2001)
- Rechtschaffen, A., Gilliland, M. A., Bergmann, B. M. & Winter, J. B. Physiological correlates of prolonged sleep deprivation in rats. Science 221, 182–184 (1983) · DOI · Paper page
- Sapolsky, R. M. Stress hormones: good and bad. Neurobiol. Dis. 7, 540–542 (2000) · DOI
- Ashburner, M. Patterns of puffing activity in the salivary gland chromosomes of Drosophila. Chromosoma 31, 356–376 (1970) · DOI
- Marchler, G. & Wu, C. Modulation of Drosophila heat shock transcription factor activity by the molecular chaperone DROJ1. EMBO J. 20, 499–509 (2001) · DOI
- Ornelles, D. A. & Penman, S. Prompt heat-shock and heat-shifted proteins associated with the nuclear matrix–intermediate filament scaffold in Drosophila melanogaster cells. J. Cell Sci. 95, 393–404 (1990) · DOI
- Cirelli, C. & Tononi, G. Gene expression in the brain across the sleep–waking cycle. Brain Res. 885, 303–321 (2000) · DOI
- Yoshida, E. N., Benkel, B. F., Fong, Y. & Hickey, D. A. Sequence and phylogenetic analysis of the SNF4/AMPK gamma subunit gene from Drosophila melanogaster. Genome 42, 1077–1087 (1999) · DOI
- Ma, E. & Haddad, G. G. Isolation and characterization of the hypoxia-inducible factor 1β in Drosophila melanogaster. Brain Res. Mol. Brain Res. 73, 11–16 (1999) · DOI
- Cornelius, G. & Engel, M. Stress causes induction of MAP kinase-specific phosphatase and rapid repression of MAP kinase activity in Drosophila. Cell Signal. 7, 611–615 (1995) · DOI
- Ekengren, S. et al. A humoral stress response in Drosophila. Curr. Biol. 11, 714–718 (2001) · DOI
- Perezgasga, L., Segovia, L. & Zurita, M. Molecular characterization of the 5′ control region and of two lethal alleles affecting the hsp60 gene in Drosophila melanogaster. FEBS Lett. 456, 269–273 (1999) · DOI
- Hogenesch, J. B. et al. Characterization of a subset of the basic-helix–loop–helix-PAS superfamily that interacts with components of the dioxin signalling pathway. J. Biol. Chem. 272, 8581–8593 (1997) · DOI
- Rechtschaffen, A. Current perspectives on the function of sleep. Perspect. Biol. Med. 41, 359–390 (1998) · DOI
- Rechtschaffen, A., Bergmann, B. M., Everson, C. A., Kushida, C. A. & Gilliland, M. A. Sleep deprivation in the rat: X. Integration and discussion of the findings. Sleep 12, 68–87 (1989) · DOI
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Self-citation
Metadata
- Authors
- Shaw, P. J., Tononi, G., Greenspan, R. J., & Robinson, D. F.
- Affiliations
- Neurosciences Institute (US)
- University of Wisconsin–Madison (US)
- Venue
- Nature
- Published
- 2002-05
- Volume
- 417
- Issue
- 6886
- Pages
- 287-291
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1987605400
- Cited by
- 488
- References
- 0
- Citations by year
- 2026: 19 · 2025: 27 · 2024: 19 · 2023: 17 · 2022: 19 · 2021: 20 · 2020: 25 · 2019: 26 · 2018: 18 · 2017: 20 · 2016: 23 · 2015: 28 · 2014: 19 · 2013: 25 · 2012: 13
- FWCI
- 8.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Neurosciences Research Foundation
- Neurosciences Foundation
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- sleep deprivation, sleep homeostasis, circadian clock, cycle gene, period, TIMELESS, clocks, heat shock genes, Hsp83, stress response genes, lethality, Drosophila
- MeSH terms
- Animals, Circadian Rhythm, Darkness, Dehydration, Drosophila melanogaster, Female, Food Deprivation, Gene Expression Regulation, Genes, Lethal, Heat-Shock Proteins, Homeostasis, Light, Mutation, Nuclear Proteins, Sleep, Sleep Deprivation, Stress, Physiological, Wakefulness, Trans-Activators, Survival Rate, Genes, Insect, Oxidative Stress, Heat-Shock Response, Insect Proteins, Drosophila Proteins, Basic Helix-Loop-Helix Proteins, CLOCK Proteins, ARNTL Transcription Factors, Period Circadian Proteins
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