The impact of sleep disruption on mouse physiology, behavior, and welfare

Laboratory mice are nocturnal, spending most of their daylight hours asleep. But they live in the diurnal world of human investigators and husbandry staff, who primarily work during this rest period. In humans, lack of sleep or sleep that occurs outside the normal circadian sleep period (as in shift work) has adverse effects. These include increased risk of cardiovascular disease, cancer, metabolic disorder, mood disorders, type II diabetes, and obesity. However, it is unknown if mice experience sleep disruption due to these human activities, and, if so, what the adverse effects may be. This is an important question, not only to ensure good welfare for laboratory mice, but also to improve experimental validity. If researchers are inadvertently inducing physiological or cognitive changes in mice through sleep disruption, we may be confounding experimental results in unpredictable fashions. This is particularly relevant to biomedical research, as only eleven percent of drug trials that pass the animal testing stage go on to pass human trials. Part of this discrepancy may be due to sleep disruption-induced changes in mice. In Chapter 2, we tested two different disruption times, one during the day (their rest period) and one at night (their active period). These changes in disruption time produced no differences in overall amounts of sleep, though there were changes in sleep timing based on sex and type of mouse. These results suggest that disturbance timing does affect sleep, but that response isn’t uniform across strains or sexes. However, it is possible that our brief welfare checks may have been too predictable and inconsequential to induce true sleep disruption. In light of these results, our next experiment (Chapter 3) involved testing more extensive and unpredictable disruptions, as well as using both physiological and behavioral measures, as well as sleep monitoring. In this project, mice were exposed to either a week of predictable disruptions, or a week of those same disruptions, consolidated at the beginning and the end of the day. After 4 days of disruption, we performed a biopsy punch procedure on them to assess wound healing, with mice being assigned to an analgesia or control group. Again, overall sleep did not change for mice in response to disruption. They did, however, display a decrease in activity levels, likely due to the stress of handling and restraint for manual analgesia injection. Additionally, male mice who received analgesia spent more time sleeping than their female counterparts, suggesting that an adequate dose for males may not be sufficient for pain relief in females