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0022 MICRORNAS ARE CROSS-SPECIES MARKERS OF SLEEP LOSS IN HUMANS AND RATS
Abstract   Open access

0022 MICRORNAS ARE CROSS-SPECIES MARKERS OF SLEEP LOSS IN HUMANS AND RATS

N Goel, D M Taylor, T Abel, W D Killgore, J Pearson-Leary and S Bhatnagar
Sleep (New York, N.Y.), Vol.40(suppl_1), pp.A8-A8
04/28/2017
DOI: 10.1093/sleepj/zsx050.021
url
https://doi.org/10.1093/sleepj/zsx050.021View
Published (Version of record) Open Access

Abstract

Abstract Introduction: Sleep loss is increasingly associated with diabetes, cancer, cardiovascular disease and Alzheimer’s disease. MicroRNAs (miRs), small non-coding RNAs that are important regulators of gene expression, typically repress the expression of their target mRNAs, and play an established role in these diseases. To determine whether miRs are involved in sleep regulation, we examined whether they change as a function of sleep loss and recovery in humans and rats. Methods: Three laboratory studies were performed, two employing sleep restriction (SR) and one employing total sleep deprivation (TSD). In Study 1, 15 healthy adults (35.0 ± 9.9y; 6 females), participated in a SR protocol: miR blood samples were taken after one 10h time-in-bed (TIB) baseline night; five 4h TIB SR nights; and one 12h TIB recovery night. In Study 2, 15 adult Sprague Dawley rats (d65-70; 8 females) participated in a SR protocol: miR samples were taken after one baseline night, four 4h TIB SR nights, and one recovery night. In Study 3, 12 healthy adults (24.8 ± 5.4y; 6 females), participated in a TSD protocol: miR samples were taken after baseline, one TSD night, and recovery. MiRs from plasma were analyzed via Affymetrix microarrays (Studies 1 and 2) or via RNA-seq (Study 3). Mixed linear models with Z-score log2 fold change cutoffs of ±1.645 and greater (FDR< 0.05) were used for statistical analysis. Results: Across the studies, 46 miRs showed significant fold changes with sleep loss, with the majority of these returning to baseline after recovery sleep. Notably, 117 gene targeted by miRs (determined from TargetScan) showed overlap across the three studies. Conclusion: These results provide the first experimental evidence miRs can track sleep loss and recovery dynamics across species and serve as epigenetic biomarkers of sleep debt. This work establishes a potential link between miR expression and known diseases resulting from sleep loss. Support (If Any): Work supported by Office of Naval Research Award No. N00014-11-1-0361 (NG); NASA NNX14AN49G (NG); Clinical and Translational Research Center (CTRC) grant UL1TR000003; Defense Advanced Research Projects Agency (DARPA) and the U.S. Army Research Office (W911NF1010093; SB, TA), and DARPA Young Faculty Award D12AP00241 (WDK).

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