Leise Tanya L, Goldberg Ariella, Michael John, Montoya Grace, Solow Sabrina, Molyneux Penny, Vetrivelan Ramalingam, Harrington Mary E
Department of Mathematics and Statistics, Amherst College, Amherst, Massachusetts.
Neuroscience Program, Smith College, Northampton, Massachusetts.
Eur J Neurosci. 2020 Jun;51(12):2343-2354. doi: 10.1111/ejn.14179. Epub 2018 Oct 22.
A single phase advance of the light:dark (LD) cycle can temporarily disrupt synchrony of neural circadian rhythms within the suprachiasmatic nucleus (SCN) and between the SCN and peripheral tissues. Compounding this, modern life can involve repeated disruptive light conditions. To model chronic disruption to the circadian system, we exposed male mice to more than a month of a 20-hr light cycle (LD10:10), which mice typically cannot entrain to. Control animals were housed under LD12:12. We measured locomotor activity and body temperature rhythms in vivo, and rhythms of PER2::LUC bioluminescence in SCN and peripheral tissues ex vivo. Unexpectedly, we discovered strong effects of the time of dissection on circadian phase of PER2::LUC bioluminescent rhythms, which varied across tissues. White adipose tissue was strongly reset by dissection, while thymus phase appeared independent of dissection timing. Prior light exposure impacted the SCN, resulting in strong resetting of SCN phase by dissection for mice housed under LD10:10, and weak phase shifts by time of dissection in SCN from control LD12:12 mice. These findings suggest that exposure to circadian disruption may desynchronize SCN neurons, increasing network sensitivity to perturbations. We propose that tissues with a weakened circadian network, such as the SCN under disruptive light conditions, or with little to no coupling, for example, some peripheral tissues, will show increased resetting effects. In particular, exposure to light at inconsistent circadian times on a recurring weekly basis disrupts circadian rhythms and alters sensitivity of the SCN neural pacemaker to dissection time.
光暗（LD）周期的单次提前会暂时破坏视交叉上核（SCN）内以及SCN与外周组织之间神经昼夜节律的同步性。更复杂的是，现代生活可能涉及反复出现的干扰性光照条件。为了模拟对昼夜节律系统的慢性干扰，我们将雄性小鼠暴露于超过一个月的20小时光照周期（LD10:10）中，而小鼠通常无法适应这种周期。对照动物饲养在LD12:12条件下。我们在体内测量了运动活动和体温节律，并在体外测量了SCN和外周组织中PER2::LUC生物发光的节律。出乎意料的是，我们发现解剖时间对PER2::LUC生物发光节律的昼夜相位有强烈影响，且这种影响在不同组织中有所不同。白色脂肪组织在解剖时会被强烈重置，而胸腺相位似乎与解剖时间无关。先前的光照暴露会影响SCN，导致饲养在LD10:10条件下的小鼠在解剖时SCN相位被强烈重置，而对照LD12:12小鼠的SCN在解剖时相位变化较小。这些发现表明，暴露于昼夜节律干扰可能会使SCN神经元去同步化，增加网络对扰动的敏感性。我们提出，昼夜节律网络较弱的组织，如处于干扰性光照条件下的SCN，或耦合很少甚至没有耦合的组织，例如一些外周组织，将表现出增强的重置效应。特别是，每周定期在不一致的昼夜时间暴露于光照会扰乱昼夜节律，并改变SCN神经起搏器对解剖时间的敏感性。
