Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation

Abstract Background Although sleep deprivation is associated with neurobehavioral impairment that may underlie significant risks to performance and safety, there is no reliable biomarker test to detect dangerous levels of impairment from sleep loss in humans. This study employs microarrays and bioin...

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Main Authors: Hilary A. Uyhelji, Doris M. Kupfer, Vicky L. White, Melinda L. Jackson, Hans P. A. Van Dongen, Dennis M. Burian
Format: Article
Language:English
Published: BMC 2018-05-01
Series:BMC Genomics
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12864-018-4664-3
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author Hilary A. Uyhelji
Doris M. Kupfer
Vicky L. White
Melinda L. Jackson
Hans P. A. Van Dongen
Dennis M. Burian
author_facet Hilary A. Uyhelji
Doris M. Kupfer
Vicky L. White
Melinda L. Jackson
Hans P. A. Van Dongen
Dennis M. Burian
author_sort Hilary A. Uyhelji
collection DOAJ
description Abstract Background Although sleep deprivation is associated with neurobehavioral impairment that may underlie significant risks to performance and safety, there is no reliable biomarker test to detect dangerous levels of impairment from sleep loss in humans. This study employs microarrays and bioinformatics analyses to explore candidate gene expression biomarkers associated with total sleep deprivation (TSD), and more specifically, the phenotype of neurobehavioral impairment from TSD. Healthy adult volunteers were recruited to a sleep laboratory for seven consecutive days (six nights). After two Baseline nights of 10 h time in bed, 11 subjects underwent an Experimental phase of 62 h of continuous wakefulness, followed by two Recovery nights of 10 h time in bed. Another six subjects underwent a well-rested Control condition of 10 h time in bed for all six nights. Blood was drawn for measuring gene expression on days two, four, and six at 4 h intervals from 08:00 to 20:00 h, corresponding to 12 timepoints across one Baseline, one Experimental, and one Recovery day. Results Altogether 212 genes changed expression in response to the TSD Treatment, with most genes exhibiting down-regulation during TSD. Also, 28 genes were associated with neurobehavioral impairment as measured by the Psychomotor Vigilance Test. The results support previous findings associating TSD with the immune response and ion signaling, and reveal novel candidate biomarkers such as the Speedy/RINGO family of cell cycle regulators. Conclusions This study serves as an important step toward understanding gene expression changes during sleep deprivation. In addition to exploring potential biomarkers for TSD, this report presents novel candidate biomarkers associated with lapses of attention during TSD. Although further work is required for biomarker validation, analysis of these genes may aid fundamental understanding of the impact of TSD on neurobehavioral performance.
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spelling doaj.art-87b5094048414ecdb2f05b85c0dfd5c12022-12-21T17:33:12ZengBMCBMC Genomics1471-21642018-05-0119111710.1186/s12864-018-4664-3Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivationHilary A. Uyhelji0Doris M. Kupfer1Vicky L. White2Melinda L. Jackson3Hans P. A. Van Dongen4Dennis M. Burian5Civil Aerospace Medical Institute, Federal Aviation AdministrationCivil Aerospace Medical Institute, Federal Aviation AdministrationCivil Aerospace Medical Institute, Federal Aviation AdministrationSleep and Performance Research Center & Elson S. Floyd College of Medicine, Washington State UniversitySleep and Performance Research Center & Elson S. Floyd College of Medicine, Washington State UniversityCivil Aerospace Medical Institute, Federal Aviation AdministrationAbstract Background Although sleep deprivation is associated with neurobehavioral impairment that may underlie significant risks to performance and safety, there is no reliable biomarker test to detect dangerous levels of impairment from sleep loss in humans. This study employs microarrays and bioinformatics analyses to explore candidate gene expression biomarkers associated with total sleep deprivation (TSD), and more specifically, the phenotype of neurobehavioral impairment from TSD. Healthy adult volunteers were recruited to a sleep laboratory for seven consecutive days (six nights). After two Baseline nights of 10 h time in bed, 11 subjects underwent an Experimental phase of 62 h of continuous wakefulness, followed by two Recovery nights of 10 h time in bed. Another six subjects underwent a well-rested Control condition of 10 h time in bed for all six nights. Blood was drawn for measuring gene expression on days two, four, and six at 4 h intervals from 08:00 to 20:00 h, corresponding to 12 timepoints across one Baseline, one Experimental, and one Recovery day. Results Altogether 212 genes changed expression in response to the TSD Treatment, with most genes exhibiting down-regulation during TSD. Also, 28 genes were associated with neurobehavioral impairment as measured by the Psychomotor Vigilance Test. The results support previous findings associating TSD with the immune response and ion signaling, and reveal novel candidate biomarkers such as the Speedy/RINGO family of cell cycle regulators. Conclusions This study serves as an important step toward understanding gene expression changes during sleep deprivation. In addition to exploring potential biomarkers for TSD, this report presents novel candidate biomarkers associated with lapses of attention during TSD. Although further work is required for biomarker validation, analysis of these genes may aid fundamental understanding of the impact of TSD on neurobehavioral performance.http://link.springer.com/article/10.1186/s12864-018-4664-3BiomarkerNeurobehavioral impairmentPVT lapsesSleep deprivationSpeedy/RINGO
spellingShingle Hilary A. Uyhelji
Doris M. Kupfer
Vicky L. White
Melinda L. Jackson
Hans P. A. Van Dongen
Dennis M. Burian
Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation
BMC Genomics
Biomarker
Neurobehavioral impairment
PVT lapses
Sleep deprivation
Speedy/RINGO
title Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation
title_full Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation
title_fullStr Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation
title_full_unstemmed Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation
title_short Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation
title_sort exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation
topic Biomarker
Neurobehavioral impairment
PVT lapses
Sleep deprivation
Speedy/RINGO
url http://link.springer.com/article/10.1186/s12864-018-4664-3
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