Timed exercise stabilizes behavioral rhythms but not molecular programs in the brain’s suprachiasmatic clock

• Published in: iScience 2023-02, Vol.26 (2), p.106002-106002, Article 106002
• Main Authors: Hitrec, Timna, Petit, Cheryl, Cryer, Emily, Muir, Charlotte, Tal, Natalie, Fustin, Jean-Michel, Hughes, Alun T.L., Piggins, Hugh D.
• Format: Article
• Language: English
• Subjects: Behavioral neuroscience; Molecular biology; Neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106002

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. [Display omitted] •Timed exercise promotes stable behavioral rhythms in VPAC2 deficient mice•Loss of VPAC2 dysregulates the suprachiasmatic (SCN) transcriptome•Timed exercise does not restore the SCN transcriptome in VPAC2 deficient mice•Behavioral effects of timed exercise require a functional molecular clock Molecular biology; Neuroscience; Behavioral neuroscience