Abstract
Shift work and trans-time zone travel lead to insufficient sleep and numerous pathologies. Here, we examined sleep/wake dynamics during chronic exposure to environmental circadian disruption (ECD), and if chronic partial sleep loss associated with ECD influences the induction of shift-related inflammatory disorder. Sleep and wakefulness were telemetrically recorded across three months of ECD, in which the dark-phase of a light-dark cycle was advanced weekly by 6 h. A three month regimen of ECD caused a temporary reorganization of sleep (NREM and REM) and wake processes across each week, resulting in an approximately 10% net loss of sleep each week relative to baseline levels. A separate group of mice were subjected to ECD or a regimen of imposed wakefulness (IW) aimed to mimic sleep amounts under ECD for one month. Fos-immunoreactivity (IR) was quantified in sleep-wake regulatory areas: the nucleus accumbens (NAc), basal forebrain (BF), and medial preoptic area (MnPO). To assess the inflammatory response, trunk blood was treated with lipopolysaccharide (LPS) and subsequent release of IL-6 was measured. Fos-IR was greatest in the NAc, BF, and MnPO of mice subjected to IW. The inflammatory response to LPS was elevated in mice subjected to ECD, but not mice subjected to IW. Thus, the net sleep loss that occurs under ECD is not associated with a pathological immune response.
Highlights
Shift work, travel across time zones, and nontraditional lighting schedules are associated with chronic misalignment of sleep schedules with internal time-keeping systems [1,2]
Significant increases in wake were found on days 3 and 5 for both shifts. These increases were at the expense of NREM sleep which was significantly decreased on days 3 and 5 for both shifts (MANOVA main effect of day F12,60 = 7.1; p,0.001; post-hoc multiple comparisons by paired t-tests, p,0.004; Fig. 3B)
This study demonstrates the differential effects of circadian misalignment and sleep loss on pro-inflammatory responses in rodents
Summary
Travel across time zones, and nontraditional lighting schedules are associated with chronic misalignment of sleep schedules with internal time-keeping systems [1,2]. These maladaptive work-sleep schedules have escalated across the past decade [3,4], and have been linked to elevated risks for insomnia and circadian rhythm disorders [5]. Few studies in rodents have explored changes in sleep and wakefulness during exposure to ECD paradigms lasting for more than one month, which are most relevant to long-term night and rotating shift work [5]
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