Light entrainment of the SCN circadian clock and implications for personalized alterations of corticosterone rhythms in shift work and jet lag.
Light entrainment of the SCN circadian clock and implications for personalized alterations of corticosterone rhythms in shift work and jet lag.
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DOI：
10.1038/s41598-021-97019-7
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发表时间：
2021-09-09
影响因子：
4.6
通讯作者：
Androulakis IP
中科院分区：
文献类型：
--
作者：
Li Y;Androulakis IP
视交叉上核(SCN)起着中央起搏器的作用，使生理和行为振荡与昼夜(活动/不活动)转换相一致。光信号携带SCN的光敏腹外侧核(VL)的分子时钟，而后者又通过神经递质血管活性肠肽(VIP)携带到背内侧(DM)壳。贝壳将VIP节律信号转换为精氨酸加压素(AVP)的昼夜振荡，AVP最终作为神经递质信号进入下丘脑-垂体-肾上腺(HPA)轴，导致糖皮质激素的强劲昼夜分泌。在这项工作中，我们讨论了一个半机械性的数学模型，该模型反映了从SCN到HPA轴的光信号转导的基本层次结构。通过合并跨核、壳和HPA轴的相互作用，我们研究了这些耦合系统如何同步导致强大的昼夜振荡。我们的模型预测了个性化同步策略的存在，这些策略能够维持内稳态节律，同时允许对瞬时和永久性光时间表变化的不同反应。我们模拟了导致节律性扰动的不同行为情景，对系统在不同光程下的动态反应进行了详细的计算分析，并确定：(1)个体间显著的多样性和灵活性特征是对不同光程的适应；(2)个体对时差和交替轮班工作的耐受呈正相关，而对时差和瞬时轮班工作的耐受呈负相关，这表明个体维持生理节律性的能力存在权衡；(3)弱光敏感度导致昼夜灵活性降低，这意味着光疗可以成为解决轮班工作和时差相关疾病的潜在方法。最后，我们绘制了SCN内部以及SCN和HPA轴之间同步的影响图，因为它与昼夜节律灵活性的出现有关。
The suprachiasmatic nucleus (SCN) functions as the central pacemaker aligning physiological and behavioral oscillations to day/night (activity/inactivity) transitions. The light signal entrains the molecular clock of the photo-sensitive ventrolateral (VL) core of the SCN which in turn entrains the dorsomedial (DM) shell via the neurotransmitter vasoactive intestinal polypeptide (VIP). The shell converts the VIP rhythmic signals to circadian oscillations of arginine vasopressin (AVP), which eventually act as a neurotransmitter signal entraining the hypothalamic–pituitary–adrenal (HPA) axis, leading to robust circadian secretion of glucocorticoids. In this work, we discuss a semi-mechanistic mathematical model that reflects the essential hierarchical structure of the photic signal transduction from the SCN to the HPA axis. By incorporating the interactions across the core, the shell, and the HPA axis, we investigate how these coupled systems synchronize leading to robust circadian oscillations. Our model predicts the existence of personalized synchronization strategies that enable the maintenance of homeostatic rhythms while allowing for differential responses to transient and permanent light schedule changes. We simulated different behavioral situations leading to perturbed rhythmicity, performed a detailed computational analysis of the dynamic response of the system under varying light schedules, and determined that (1) significant interindividual diversity and flexibility characterize adaptation to varying light schedules; (2) an individual’s tolerances to jet lag and alternating shift work are positively correlated, while the tolerances to jet lag and transient shift work are negatively correlated, which indicates trade-offs in an individual’s ability to maintain physiological rhythmicity; (3) weak light sensitivity leads to the reduction of circadian flexibility, implying that light therapy can be a potential approach to address shift work and jet lag related disorders. Finally, we developed a map of the impact of the synchronization within the SCN and between the SCN and the HPA axis as it relates to the emergence of circadian flexibility.