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

Area of Science:

• Chronobiology
• Molecular Biology
• Neuroscience

Background:

• Circadian rhythms are crucial for physiological processes, regulated by the suprachiasmatic nuclei (SCN).
• Neuropeptide Y receptor 2 (Ynpr2) signaling is vital for maintaining circadian rhythm stability.
• Genetic impairment of Ynpr2 signaling in mice (Vipr2-/-) leads to disrupted circadian rhythms.

Purpose of the Study:

• To investigate the molecular effects of Ynpr2 deficiency and scheduled voluntary exercise (SVE) on circadian clock gene expression.
• To compare the impact of SVE on the SCN, liver, and lung transcriptomes in wild-type and Vipr2-/- mice.

Main Methods:

• Utilized RNA sequencing (RNA-seq) and quantitative reverse transcription PCR (qRT-PCR).
• Analyzed gene expression profiles in the SCN, liver, and lung tissues.
• Compared molecular responses to SVE between Vipr2-/- mice and their wild-type (Vipr2+/+) littermates.

Main Results:

• Vipr2-/- mice exhibited significant dysregulation in the SCN transcriptome, affecting core clock genes and neurochemicals.
• SVE normalized behavioral rhythms in Vipr2-/- mice but did not fully correct the SCN transcriptome.
• Peripheral tissues (liver, lung) in Vipr2-/- mice showed partially intact molecular programs, with altered responses to SVE compared to wild-type.

Conclusions:

• SVE can effectively correct behavioral arrhythmicity in mice with impaired neuropeptide signaling.
• The SCN transcriptome remains significantly altered in Vipr2-/- mice despite behavioral rhythm restoration by SVE.
• SVE influences peripheral tissue molecular programs differently in the context of neuropeptide signaling deficiency.