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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 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.

SUBMITTER: Uyhelji HA

PROVIDER: S-EPMC5941663 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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

Uyhelji Hilary A HA Kupfer Doris M DM White Vicky L VL Jackson Melinda L ML Van Dongen Hans P A HPA Burian Dennis M DM

BMC genomics 20180509 1

<h4>Background</h4>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 ad ...[more]

PMID: 29739334

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Project description:A night without sleep is followed by enhanced sleepiness, increased low-frequency activity in the waking EEG, and reduced vigilant attention. The magnitude of these changes is highly variable among healthy individuals. Findings in young men of low and high subjective caffeine sensitivity suggest that adenosinergic mechanisms contribute to inter-individual differences in sleep deprivation-induced changes in EEG theta activity, as well as optimal performance on the psychomotor vigilance task (PVT). In comparison to young subjects, healthy adults of older age typically feel less sleepy after sleep deprivation, and show fewer response lapses, and faster reaction times on the PVT, especially in the morning after the night without sleep. We hypothesized that age-related changes in adenosine signal transmission underlie reduced vulnerability to sleep deprivation in older individuals. To test this hypothesis, the combined effects of prolonged wakefulness and the adenosine receptor antagonist, caffeine, on an antero-posterior power gradient in EEG theta activity and PVT performance were analyzed in healthy older and caffeine-insensitive and -sensitive young men. The results show that age-related differences in sleep loss-induced changes in brain rhythmic activity and neurobehavioral functions are mirrored in young individuals of low and high sensitivity to the stimulant effects of caffeine. Moreover, the effects of sleep deprivation and caffeine on regional theta power and vigilant attention are inversely correlated across older and young age groups. Genetic variants of the adenosine A(2A) receptor gene contribute to individual differences in neurobehavioral performance in rested and sleep deprived state, and modulate the actions of caffeine in wakefulness and sleep. Based upon this evidence, we propose that age-related differences in A(2A) receptor-mediated signal transduction could be involved in age-related changes in the vulnerability to acute sleep deprivation.

Dataset Information

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

Publications

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

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