Rhythm-Promoting Actions of Exercise in Mice with Deficient Neuropeptide Signaling

Aug 4, 2010Journal of biological rhythms

Exercise helps restore body rhythms in mice lacking certain brain chemical signals

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Abstract

Scheduled voluntary exercise for 6 hours daily can promote improvements in circadian rhythms in genetically modified mice.

In constant dark, wild-type mice exhibit strong rhythmicity with a period of approximately 23.5 hours, while VIP(-/-) and Vipr2(-/-) mice show weak rhythms with periods of less than 23 hours.
VIP(-/-) and Vipr2(-/-) mice synchronize rapidly to scheduled voluntary exercise in less than 7 days, unlike wild-type mice, which take over 35 days.
After 21 to 50 days of scheduled voluntary exercise, most Vipr2(-/-) mice maintain near 24-hour behavioral rhythms, whereas very few VIP(-/-) mice achieve this.
Scheduled daily exercise may serve as a noninvasive intervention for improving circadian rhythms in conditions with disrupted timekeeping.

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Daily exercise promotes physical health as well as improvements in mental and neural functions. Studies in intact wild-type (WT) rodents have revealed that the brain's suprachiasmatic nuclei (SCN), site of the main circadian pacemaker, are also responsive to scheduled wheel running. It is unclear, however, if and how animals with a dysfunctional circadian pacemaker respond to exercise. Here, we tested whether scheduled voluntary exercise (SVE) in a running wheel for 6 hours per day could promote neural and behavioral rhythmicity in animals whose circadian competence is compromised through genetically targeted loss of vasoactive intestinal polypeptide (VIP(-/-) mice) or its VPAC(2) receptor (Vipr2(-/-) mice). We report that in constant dark (DD), rhythmic VIP(-/-) and Vipr2(-/-) mice show weak free-running rhythms with a period of <23 hours and all wild-type mice are strongly rhythmic with approximately 23.5-hour periodicity. VIP(-/-) and Vipr2(-/-) mice rapidly (<7 days) synchronize to daily SVE, while WT mice take much longer (>35 days). Following 21 to 50 days of SVE, WT mice show small changes in their rhythms, and most Vipr2(-/-) mice now sustain robust near 24-hour behavioral rhythms, whereas very few VIP(-/-) mice do. This study demonstrates that scheduled daily exercise can markedly improve circadian rhythms in behavioral activity and raises the possibility that this noninvasive approach may be useful as an intervention in clinical etiologies in which there are dysfunctions of circadian time keeping.

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Rhythm-Promoting Actions of Exercise in Mice with Deficient Neuropeptide Signaling

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