title: Cross-translational studies in human and Drosophila identify markers of sleep loss.
abstract: 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.
authors: Department of Anatomy and Physiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors: Matthew S
authors: MS
authors: Thimgan
authors: Laura
authors: L
authors: Gottschalk
authors: Cristina
authors: C
authors: Toedebusch
authors: Jennifer
authors: J
authors: McLeland
authors: Allan
authors: A
authors: Rechtschaffen
authors: Marcia
authors: M
authors: Gilliland-Roberts
authors: Stephen P
authors: SP
authors: Duntley
authors: Paul J
authors: PJ
authors: Shaw
mesh_terms: D000328:Adult; D000818:Animals; D017318:Annexin A3 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D057906:Circadian Clocks / Q000235:genetics; D004330:Drosophila; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008297:Male; D009154:Mutation; D051381:Rats; D012463:Saliva / Q000378:metabolism; D015398:Signal Transduction; D012892:Sleep Deprivation / Q000378:metabolism; D007319:Sleep Initiation and Maintenance Disorders / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic; D057170:Translational Research, Biomedical
chemical_list: D015415:Biomarkers; D039481:CD11b Antigen; C509295:ITGAM protein, human; D015850:Interleukin-6; D017318:Annexin A3
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