Hitrec Timna, Petit Cheryl, Cryer Emily, Muir Charlotte, Tal Natalie, Fustin Jean-Michel, Hughes Alun T L, Piggins Hugh D
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.
iScience. 2023 Jan 18;26(2):106002. doi: 10.1016/j.isci.2023.106002. eCollection 2023 Feb 17.
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 ( 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 animals, the SCN transcriptome of 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 mice were partially intact, although their response to SVE differed to that of these peripheral tissues in the mice. These findings highlight that SVE can correct behavioral abnormalities in circadian rhythms without causing large scale alterations to the SCN transcriptome.
每天定时使用跑步轮（定时自愿运动；SVE）可使啮齿动物的昼夜节律同步，并促进神经肽信号传导基因靶向损伤动物（小鼠）的稳定24小时节律。在这里，我们使用RNA测序和/或定量逆转录聚合酶链反应来评估这种神经肽信号传导损伤以及SVE如何塑造大脑生物钟（视交叉上核；SCN）和外周组织（肝脏和肺）中的分子程序。与动物相比，小鼠的SCN转录组表现出广泛的失调，包括核心生物钟成分、转录因子和神经化学物质。此外，尽管SVE使这些动物的行为节律稳定，但SCN转录组仍失调。小鼠肺和肝中的分子程序部分完整，尽管它们对SVE的反应与小鼠这些外周组织的反应不同。这些发现突出表明，SVE可以纠正昼夜节律中的行为异常，而不会导致SCN转录组的大规模改变。
