Cross-Translational Studies in Human and Drosophila Identify Markers of Sleep Loss
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Inadequate sleep has become endemic, which imposes a substantial burden for public health and safety. At present, there are no objective tests to determine if an individual has gone without sleep for an extended period of time. Here we describe a novel approach that takes advantage of the evolutionary conservation of sleep to identify markers of sleep loss. To begin, we demonstrate that IL-6 is increased in rats following chronic total sleep deprivation and in humans following 30 h of waking. Discovery experiments were then conducted on saliva taken from sleep-deprived human subjects to identify candidate markers. Given the relationship between sleep and immunity, we used Human Inflammation Low Density Arrays to screen saliva for novel markers of sleep deprivation. Integrin αM (ITGAM) and Anaxin A3 (AnxA3) were significantly elevated following 30 h of sleep loss. To confirm these results, we used QPCR to evaluate ITGAM and AnxA3 in independent samples collected after 24 h of waking; both transcripts were increased. The behavior of these markers was then evaluated further using the power of Drosophila genetics as a cost-effective means to determine whether the marker is associated with vulnerability to sleep loss or other confounding factors (e.g., stress). Transcript profiling in flies indicated that the Drosophila homologues of ITGAM were not predictive of sleep loss. Thus, we examined transcript levels of additional members of the integrin family in flies. Only transcript levels of scab, the Drosophila homologue of Integrin α5 (ITGA5), were associated with vulnerability to extended waking. Since ITGA5 was not included on the Low Density Array, we returned to human samples and found that ITGA5 transcript levels were increased following sleep deprivation. These cross-translational data indicate that fly and human discovery experiments are mutually reinforcing and can be used interchangeably to identify candidate biomarkers of sleep loss.
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Inflammatory cytokines IL-1 and TNF appear to be likely candidates in mediating sleep changes observed in HIV infection, given their sleep-modulating role in animal models and upregulation in HIV-infected patients.
“Inflammatory cytokines (e.g., IL-1 and TNF) appear to be likely candidates in mediating sleep changes observed in HIV infection, given their sleep modulating role in animal models (see sect. IIB1) and upregulation in HIV-infected patients (195, 477, 540).”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [540]
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The Sleep-Immune Crosstalk in Health and Disease
Besedovsky, L., Lange, T., & Haack, M. (2019) · Physiological Reviews · doi:10.1152/physrev.00010.2018 · Cited by 1,479 · see citing works
Developing Biomarker Arrays Predicting Sleep and Circadian-Coupled Risks to Health
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- Authors
- Thimgan, M. S., Gottschalk, L., Toedebusch, C., McLeland, J., Rechtschaffen, A., Gilliland-Roberts, M., Duntley, S. P., & Shaw, P. J.
- Affiliations
- Washington University in St. Louis (US)
- University of Chicago (US)
- Corresponding author
- Shaw, Paul J.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-04-24
- Volume
- 8
- Issue
- 4
- Pages
- e61016
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3634862
- OpenAlex
- W2087008795
- Cited by
- 26
- References
- 61
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 5 · 2015: 4 · 2014: 5
- FWCI
- 6.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Knowledge@UChicago (University of Chicago) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- University of Chicago (cc-by)
- Funders
- W. M. Keck Foundation
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R21HL092731)
- National Institute of Neurological Disorders and Stroke (R01NS051305)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- sleep deprivation, salivary biomarkers, scab, Drosophila model, interleukin-6, inflammation
- MeSH terms
- Adult, Animals, Drosophila, Female, Humans, Inflammation, Sleep Initiation and Maintenance Disorders, Male, Mutation, Saliva, Sleep Deprivation, Transcription, Genetic, Signal Transduction, Biomarkers, Interleukin-6, Annexin A3, Gene Expression Profiling, CD11b Antigen, Rats, Translational Research, Biomedical, Circadian Clocks
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