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The peripheral genome-wide gene expression profiles in humans after prolonged wakefulness and sleep recovery

ABSTRACT: Although the specific functions of sleep have not been completely elucidated, the literature has suggested that sleep is essential for proper homeostasis. Sleep loss is associated with changes in behavioral, neurochemical, cellular, and metabolic function as well as impaired immune response. We evaluated the gene expression profiles of healthy male volunteers who underwent 60 hours of prolonged wakefulness (PW) followed by 12 hours of sleep recovery (SR) using high-resolution microarrays. Peripheral whole blood was collected at 8 am in the morning before the initiation of PW (baseline), after the second night of PW, and one night after SR. We identified over 500 genes that were differentially expressed. Notably, these genes were related to DNA damage and repair and stress response as well diverse immune system responses such as natural killer pathways including killer cell lectin-like receptors family, as well granzymes and T-cell receptors which play important roles in host defense. These results support the idea that sleep loss can lead to alterations in molecular processes that result in perturbation of cellular immunity, induction of inflammatory responses, and homeostatic imbalance. Moreover, expression of multiple genes was down-regulated following PW and up-regulated after SR compared to PW, suggesting an attempt of the body to re-establish internal homeostasis. In silico validation of alterations in the expression of CETN3, DNAJC and CEACAM genes, confirmed previous findings related to the molecular effects of sleep deprivation. Thus, the present findings confirm that the effects of sleep loss are not restricted to the brain and can occur intensely in peripheral tissues.

ORGANISM(S): Homo sapiens

PROVIDER: GSE37667 | GEO | 2012/05/02

SECONDARY ACCESSION(S): PRJNA162889

REPOSITORIES: GEO

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Project description:Although the specific functions of sleep have not been completely elucidated, the literature has suggested that sleep is essential for proper homeostasis. Sleep loss is associated with changes in behavioral, neurochemical, cellular, and metabolic functions as well as impaired immune response. We evaluated the gene expression profiles of healthy volunteers submitted to 48 hours of prolonged wakefulness (PW) followed by 12 hours of sleep recovery (SR) using high-resolution microarrays. Peripheral whole blood was collected in the morning before the initiation of sleep deprivation (baseline), after the second night of PW, and one night after SR. the identified differentially expressed genes were related to immune response, DNA damage and repair as well as inflammation. Examples of these include: killer cell lectin-like receptors family granzymes and T-cell receptors, which play important roles in host defense. These results support the idea that sleep loss can lead to alteration of molecular processes that drive perturbation of cellular immunity, induction of inflammatory response and homeostatic imbalance. Moreover, down-regulation of multiple genes after prolonged wakefulness (in comparison with baseline condition) and up-regulated after sleep recovery (in comparison with prolonged wakefulness condition) were observed, suggesting an attempt of the body to re-establish internal homeostasis. In silico validation of alterations in the expression of CETN3, DNAJC, IGFR2B and CEACAM genes, confirmed the previous findings related to the molecular effects of sleep deprivation. It is clear that confirmatory studies will be necessary to fully validate the potential candidate genes and functional networks identified. Nevertheless, the present findings confirm that the effects of sleep deprivation are not restricted to the brain and can occur intensely in peripheral tissues. The peripheral blood from each volunteer (nine individuals) were collected in the baseline night and every morning after PW and after the night of SR.

Project description:Sleep is essential for life. A good night's sleep is pleasurable and sleep deprivation is stressful. Prolonged sleep loss impairs temperature control, metabolism, immunity, and ultimately leads to death. Extensive observational and epidemiological evidence indicates that optimal sleep duration of 8 hours is associated with the maintenance of good health. In our society, however, most people only get 6.5 - 7 hours. Suboptimal sleep duration has a strong association with mortality and morbidity. Lack of sleep has been linked to cardiovascular diseases, obesity, hypertension, type 2 diabetes, and other health/cognition conditions. It is clear that the biological need for sleep varies dramatically among humans. Sleep and circadian disorders can include Familial Advanced Sleep Phase (FASP), Delayed Sleep Phase (DSP), Advanced Sleep Phase (ASP), Natural Short Sleepers (NSS) or Long Sleeping. In example, Natural Short Sleepers (NSS) have a lifelong tendency to sleep only 4 - 6 hours per night and to awaken refreshed and energetic. Natural Long Sleepers biologically require 9 - 10 hours/night to feel well rested. The 'Sleep and Circadian Disorders Study' (SACDS) at the University of California San Francisco, set out to investigate the mechanisms involved in regulating sleep duration, patterns and sleep quality regulation by identifying and characterization of individuals and families with unusual sleep and circadian rhythm behavior patterns. SACDS participants were screened with a "General Sleep Questionnaire" that inquired about multiple aspects of sleep, including habitual work-day versus non-work day sleep-wake schedules, permits calculation of subjective habitual initial sleep onset, final sleep offset, and number of awakenings. There was an additional screening process including demographic data, sleep, mood, behavioral and general medical questionnaires, plus the study consent. After the extensive screening of 117 participants, blood samples were collected from 38 individuals and of those 10 samples were chosen for whole exome sequencing analysis.

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The peripheral genome-wide gene expression profiles in humans after prolonged wakefulness and sleep recovery

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