A Rodent Model of Night-Shift Work Induces Short-Term and Enduring Sleep and Electroencephalographic Disturbances

Abstract

Millions of people worldwide are working at times that overlap with the normal time for sleep. Sleep problems related to the work schedule may mediate the well-established relationship between shift work and increased risk for disease, occupational errors and accidents. Yet, our understanding of causality and the underlying mechanisms that explain this relationship is limited. We aimed to assess the consequences of night-shift work for sleep and to examine whether night-shift work-induced sleep disturbances may yield electrophysiological markers of impaired maintenance of the waking brain state. An experimental model developed in rats simulated a 4-day protocol of night-work in humans. Two groups of rats underwent 8-h sessions of enforced ambulation, either at the circadian time when the animal was physiologically primed for wakefulness (active-workers, mimicking day-shift) or for sleep (rest-workers, mimicking night-shift). The 4-day rest-work schedule induced a pronounced redistribution of sleep to the endogenous active phase. Rest-work also led to higher electroencephalogram (EEG) slow-wave (1-4 Hz) energy in quiet wakefulness during work-sessions, suggesting a degraded waking state. After the daily work-sessions, being in their endogenous active phase, rest-workers slept less and had higher gamma (80-90 Hz) activity during wake than active-workers. Finally, rest-work induced an enduring shift in the main sleep period and attenuated the accumulation of slow-wave energy during NREM sleep. A comparison of recovery data from 12:12 LD and constant dark conditions suggests that reduced time in NREM sleep throughout the recorded 7-day recovery phase induced by rest-work may be modulated by circadian factors. Our data in rats show that enforced night-work-like activity during the normal resting phase has pronounced acute and persistent effects on sleep and waking behavior. The study also underscores the potential importance of animal models for future studies on the health consequences of night-shift work and the mechanisms underlying increased risk for diseases.

Shift in Food Intake and Changes in Metabolic Regulation and Gene Expression during Simulated Night-Shift Work: A Rat Model

“…Despite this reduction in energy intake between work sessions, body weight increased between sessions, presumably because the lower energy intake was compensated for by parallel reduction in energy expenditure. In agreement with this, RW body temperature was decreased between sessions, perhaps partly as a consequence of increased sleep [23]. This possibly represents a compensatory mechanism aimed at maintaining body weight.…”

“…To mimic human shift work and compare this with normal daytime work, rats were exposed to forced activity for 8 h per day, centred either during the rats’ normal active phase (AW; ZT 14-22) or during the rats’ normal rest phase (RW; ZT 2-10), as described previously [23]. Forced activity was achieved by placing the rats in automatically rotating wheels (Rat Running Wheel, TSE running wheel system, Bad Homburg, Germany; 24 cm diameter; 3 rpm; 1440 revolutions or 1.086 km of linear distance per 8 h session).…”

No Escaping the Rat Race: Simulated Night Shift Work Alters the Time-of-Day Variation in BMAL1 Translational Activity in the Prefrontal Cortex

“…Additionally, expression of dominant-negative S6K1 mutant in rat medial PFC resulted in less active coping behavior in the forced swim test (Dwyer et al, 2015 ). It is tempting to speculate that disruption of these processes may contribute to the degraded waking state observed in rats exposed to simulated night shift work (Grønli et al, 2017 ).…”

“…We have recently established a rat model of shift work, where rats are exposed to enforced ambulation in slowly rotating wheels for 8 h/day, either in their rest phase (“rest work”; to simulate night shift work) or in their active phase (“active work”; to simulate day shift work; Marti et al, 2016 ; Grønli et al, 2017 ). Using this model, we observed a progressive intrusion of spontaneous cortical slow waves and micro-sleeps during rest work across four consecutive days, which was not observed during active work (Grønli et al, 2017 ). Similar findings have been observed in human studies, and likely contribute to decreased alertness during the night shift (Torsvall and Åkerstedt, 1987 ; Torsvall et al, 1989 ).…”

Skiftarbeid, døgnrytmer og søvn

“…Forsøk på rotter som har «jobbet» om natten viser også at selv om de sover like lenge som dagarbeidere er våkenhetsfunksjonen om natten påvirket. Dette viser seg som sakte hjernebølger under våkenhet, slike man vanligvis ser under søvn (12). Dette forteller oss at døgnrytmen spiller en viktig rolle for hjernens funksjon.…”