该研究评估了环境毒物的影响,如多环芳烃(PAHs),脑内皮细胞的昼夜节律调节和功能,构成血脑屏障(BBB)的主要结构元素。PAH是在人和动物组织中积累的亲脂性和高毒性的环境污染物。与气候变化有关的环境因素,例如野火的频率和强度的增加或飓风或热带气旋的强度的增强,可能导致这些有毒物质的重新分配和增加人类暴露。这些自然灾害还与受影响人群的昼夜节律中断有关,将环境毒物暴露的增加与昼夜节律途径的改变联系起来。几个重要的生理过程由昼夜节律协调,昼夜节律时钟的中断可能导致几种疾病的发展。血脑屏障(BBB)对于保护大脑免受血液传播的有害物质至关重要,它的完整性受到昼夜节律的影响。脑内皮细胞暴露于人类和环境相关的PAH混合物导致关键昼夜节律调节剂表达的剂量依赖性改变,比如时钟,Bmal1、Cry1/2和Per1/2。此外,昼夜节律时钟基因的沉默增强了PAHs对主要紧密连接基因和蛋白质表达的影响(即,claudin-5,occludin,JAM-2和ZO-2),以及线粒体生物能学。这项研究的发现有助于更好地理解PAH引起的健康影响的病理影响,尤其是那些与昼夜节律中断有关的。
The study evaluates the impact of environmental toxicants, such as polycyclic aromatic hydrocarbons (PAHs), on circadian regulations and functions of brain endothelial cells, which form the main structural element of the blood-brain barrier (BBB). PAH are lipophilic and highly toxic environmental pollutants that accumulate in human and animal tissues. Environmental factors related to climate change, such as an increase in frequency and intensity of wildfires or enhanced strength of hurricanes or tropical cyclones, may lead to redistribution of these toxicants and enhanced human exposure. These natural disasters are also associated with disruption of circadian rhythms in affected populations, linking increased exposure to environmental toxicants to alterations of circadian rhythm pathways. Several vital physiological processes are coordinated by circadian rhythms, and disruption of the circadian clock can contribute to the development of several diseases. The blood-brain barrier (BBB) is crucial for protecting the brain from blood-borne harmful substances, and its integrity is influenced by circadian rhythms. Exposure of brain endothelial cells to a human and environmentally-relevant PAH mixture resulted in dose-dependent alterations of expression of critical circadian modulators, such as Clock, Bmal1, Cry1/2, and Per1/2. Moreover, silencing of the circadian Clock gene potentiated the impact of PAHs on the expression of the main tight junction genes and proteins (namely, claudin-5, occludin, JAM-2, and ZO-2), as well as mitochondrial bioenergetics. Findings from this study contribute to a better understanding of pathological influence of PAH-induced health effects, especially those related to circadian rhythm disruption.