Voluntary scheduled exercise alters diurnal rhythms of behaviour, physiology and gene expression in wild-type and vasoactive intestinal peptide-deficient mice.

Key points The circadian system drives rhythms of behaviour, physiology and gene expression in alignment to a lightdark cycle, and misalignment of the internal clock with the external environment can lead to disease. We sought to determine whether scheduled exercise could alter rhythmic properties in mice while subjected to the strong entrainment effects of light and whether we could improve diurnal deficits observed in the vasointestinal polypeptide (VIP)-deficient mouse. Scheduled exercise altered daily rhythms of activity, physiology and gene expression in wild-type and VIP-deficient mice. Scheduled exercise during the late night improved many of the rhythmic deficits observed in VIP-deficient mice, including changes in gene expression within the suprachiasmatic nucleus, the site of circadian rhythm generation. The results raise the possibility that scheduled exercise could be a tool to drive and improve daily rhythms in humans to mitigate the negative consequences of circadian misalignment. Abstract The circadian system co-ordinates the temporal patterning of behaviour and many underlying biological processes. In some cases, the regulated outputs of the circadian system, such as activity, may be able to feed back to alter core clock processes. In our studies, we used four wheel-access conditions (no access; free access; early night; and late night) to manipulate the duration and timing of activity while under the influence of a lightdark cycle. In wild-type mice, scheduled wheel access was able to increase ambulatory activity, inducing a level of exercise driven at various phases of the lightdark cycle. Scheduled exercise also manipulated the magnitude and phasing of the circadian-regulated outputs of heart rate and body temperature. At a molecular level, the phasing and amplitude of PER2::LUCIFERASE (PER2::LUC) expression rhythms in the SCN and peripheral tissues of Per2::Luc knockin mice were altered by scheduled exercise. We then tested whether scheduled wheel access could improve deficits observed in vasointestinal polypeptide-deficient mice under the influence of a lightdark cycle. We found that scheduled wheel access during the late night improved many of the behavioural, physiological and molecular deficits previously described in vasointestinal polypeptide-deficient mice. Our results raise the possibility that scheduled exercise could be used as a tool to modulate daily rhythms and, when applied, may counteract some of the negative impacts of ageing and disease on the circadian system.