Chronobiology Unit, Groningen Institute for Evolutionary Life Sciences, University of Groningen, the Netherlands; School of Medicine, Hunan Normal University, Changsha, PR China.
Chronobiology Unit, Groningen Institute for Evolutionary Life Sciences, University of Groningen, the Netherlands.
Horm Behav. 2023 Apr;150:105326. doi: 10.1016/j.yhbeh.2023.105326. Epub 2023 Feb 8.
While stress does not affect the phase or period of the central pacemaker in the suprachiasmatic nucleus, it can shift clocks in peripheral tissues. Our previous studies showed significant delays of the PER2 rhythms in lung and kidney following social defeat stress. The mechanism underlying these effects is not fully understood, but might involve glucocorticoids (GC) released during the stressor. In the present study, we performed social defeat stress in adrenalectomized (ADX) mice to see if the induction of endogenous GC is necessary for the stress-induced phase shifts of peripheral clocks. We used mice that carry a luciferase reporter gene fused to the circadian clock gene Period2 (PER2::LUC) to examine daily rhythms of PER2 expression in various peripheral tissues. Mice were exposed to 5 consecutive daily social defeat stress in the late dark phase (ZT21-22). Running wheel rotations were recorded during 7 baseline and 5 social defeat days, which showed that social defeat stress suppressed locomotor activity without affecting the phase of the rhythm. This suppression of activity was not prevented by ADX. One hour after the last stressor, tissue samples from the liver, kidney and lung were collected and cultured for ex vivo bioluminescence recordings. In the liver, PER2 rhythms were not affected by social defeat stress or ADX. In the kidney, social defeat stress caused a > 4 h phase delay of the PER2 rhythm, which was prevented by ADX, supporting the hypothesis of a crucial role of GC in this stress effect. In the lung, social defeat stress caused an 8 h phase delay, but, surprisingly, a similar phase delay was seen in ADX animals independent of defeat. The latter indicates complex effects of stress and stress hormones on the lung clock. In conclusion, the findings show that repeated social defeat stress in the dark phase can shift PER2 rhythms in some tissues (lung, kidney) and not others (liver). Moreover, the social defeat stress effect in some tissues appears to be mediated by glucocorticoids (kidney) whereas the mechanism in other tissues is more complex (lung).
虽然压力不会影响视交叉上核中央起搏器的相位或周期，但它可以改变周围组织中的时钟。我们之前的研究表明，社交挫败应激后，肺和肾中的 PER2 节律明显延迟。这些影响的机制尚不完全清楚，但可能涉及应激期间释放的糖皮质激素（GC）。在本研究中，我们对肾上腺切除术（ADX）小鼠进行社交挫败应激，以观察内源性 GC 的诱导是否是周围时钟应激诱导相位变化所必需的。我们使用携带与昼夜节律基因 PER2 融合的荧光素酶报告基因的小鼠（PER2::LUC）来检查各种外周组织中 PER2 表达的日常节律。小鼠在暗期晚期（ZT21-22）连续 5 天接受社交挫败应激。在 7 个基线日和 5 个社交挫败日期间记录跑步轮旋转，结果表明社交挫败应激抑制了运动活动，而不影响节律的相位。ADX 并不能防止这种活动的抑制。最后一次应激后 1 小时，采集肝脏、肾脏和肺组织样本进行离体生物发光记录。在肝脏中，社交挫败应激对 PER2 节律没有影响，也不受 ADX 的影响。在肾脏中，社交挫败应激导致 PER2 节律的相位延迟>4 小时，ADX 可防止这种情况，支持 GC 在这种应激效应中起关键作用的假设。在肺部，社交挫败应激导致相位延迟 8 小时，但令人惊讶的是，ADX 动物中也观察到类似的相位延迟，而这种延迟与挫败无关。后者表明应激和应激激素对肺时钟的复杂影响。总之，这些发现表明，在暗期反复进行社交挫败应激可以改变一些组织（肺、肾）中的 PER2 节律，但不会改变其他组织（肝）中的 PER2 节律。此外，一些组织中的社交挫败应激效应似乎是由糖皮质激素（肾）介导的，而其他组织中的机制则更为复杂（肺）。
