Timed exercise stabilizes behavioral rhythms but not molecular programs in the brain’s suprachiasmatic clock
Timna Hitrec,
Cheryl Petit,
Emily Cryer,
Charlotte Muir,
Natalie Tal,
Jean-Michel Fustin,
Alun T.L. Hughes,
Hugh D. Piggins
Affiliations
Timna Hitrec
School of Physiology, Pharmacology, and Neuroscience, Faculty of Life Sciences, University of Bristol, Bristol BS8 1TD, UK
Cheryl Petit
School of Medical Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester M13 9PT, UK
Emily Cryer
School of Biological Sciences, Faculty of Life Sciences, University of Bristol, Bristol BS8 1TQ, UK
Charlotte Muir
School of Physiology, Pharmacology, and Neuroscience, Faculty of Life Sciences, University of Bristol, Bristol BS8 1TD, UK
Natalie Tal
School of Medical Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester M13 9PT, UK
Jean-Michel Fustin
School of Medical Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester M13 9PT, UK
Alun T.L. Hughes
School of Medical Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester M13 9PT, UK; School of Biological and Environmental Sciences, Faculty of Science, Liverpool John Moores University, Liverpool L3 3AF, UK; Corresponding author
Hugh D. Piggins
School of Physiology, Pharmacology, and Neuroscience, Faculty of Life Sciences, University of Bristol, Bristol BS8 1TD, UK; School of Medical Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester M13 9PT, UK; Corresponding author
Summary: Timed daily access to a running-wheel (scheduled voluntary exercise; SVE) synchronizes rodent circadian rhythms and promotes stable, 24h rhythms in animals with genetically targeted impairment of neuropeptide signaling (Vipr2−/− mice). Here we used RNA-seq and/or qRT-PCR to assess how this neuropeptide signaling impairment as well as SVE shapes molecular programs in the brain clock (suprachiasmatic nuclei; SCN) and peripheral tissues (liver and lung). Compared to Vipr2+/+ animals, the SCN transcriptome of Vipr2−/− mice showed extensive dysregulation which included core clock components, transcription factors, and neurochemicals. Furthermore, although SVE stabilized behavioral rhythms in these animals, the SCN transcriptome remained dysregulated. The molecular programs in the lung and liver of Vipr2−/− mice were partially intact, although their response to SVE differed to that of these peripheral tissues in the Vipr2+/+ mice. These findings highlight that SVE can correct behavioral abnormalities in circadian rhythms without causing large scale alterations to the SCN transcriptome.