Institute of Anatomy II, Medical Faculty, Heinrich-Heine-University (HHU), 40225 Düsseldorf, Germany.
Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf (UKE), Martinistraße 52, 20251 Hamburg, Germany.
Cells. 2023 Jul 12;12(14):1836. doi: 10.3390/cells12141836.
In mammals, the circadian system controls various physiological processes to maintain metabolism, behavior, and immune function during a daily 24 h cycle. Although driven by a cell-autonomous core clock in the hypothalamus, rhythmic activities are entrained to external cues, such as environmental lighting conditions. Exposure to artificial light at night (ALAN) can cause circadian disruption and thus is linked to an increased occurrence of civilization diseases in modern society. Moreover, alterations of circadian rhythms and dysregulation of immune responses, including inflammasome activation, are common attributes of neurodegenerative diseases, including Alzheimer', Parkinson's, and Huntington's disease. Although there is evidence that the inflammasome in the hippocampus is activated by stress, the direct effect of circadian disruption on inflammasome activation remains poorly understood. In the present study, we aimed to analyze whether exposure to constant light (LL) affects inflammasome activation in the mouse hippocampus. In addition to decreased circadian power and reduced locomotor activity, we found cleaved caspase 1 significantly elevated in the hippocampus of mice exposed to LL. However, we did not find hallmarks of inflammasome priming or cleavage of pro-interleukins. These findings suggest that acute circadian disruption leads to an assembled "ready to start" inflammasome, which may turn the brain more vulnerable to additional aversive stimuli.
在哺乳动物中,生物钟系统控制着各种生理过程,以维持代谢、行为和免疫功能在每天 24 小时的周期内正常运行。尽管下丘脑的细胞自主核心时钟驱动着生物钟,但有节奏的活动会被外部线索(如环境光照条件)重新调整。夜间暴露在人工光(ALAN)下会导致生物钟紊乱,从而增加现代社会文明病的发生。此外,昼夜节律的改变和免疫反应的失调,包括炎性小体的激活,是神经退行性疾病(包括阿尔茨海默病、帕金森病和亨廷顿病)的共同特征。虽然有证据表明,应激会激活海马体中的炎性小体,但昼夜节律紊乱对炎性小体激活的直接影响仍知之甚少。在本研究中,我们旨在分析持续光照(LL)暴露是否会影响小鼠海马体中的炎性小体激活。除了昼夜节律功率降低和运动活性减少外,我们还发现暴露于 LL 的小鼠海马体中 cleaved caspase 1 显著升高。然而,我们没有发现炎性小体引发或前白细胞介素切割的特征。这些发现表明,急性昼夜节律紊乱导致组装成“准备启动”的炎性小体,这可能使大脑更容易受到额外的不良刺激。