The choroid plexus (ChP) in the brain ventricles has a major influence on brain homeostasis. In this study, we aimed to determine whether the circadian clock located in ChP is affected by chronodisruption caused by misalignment with the external light/dark cycle and/or inflammation. Adult mPer2^Luc mice were maintained in the LD12:12 cycle or exposed to one of two models of chronic chronodisruption – constant light for 22–25 weeks (cLL) or 6-hour phase advances of the LD12:12 cycle repeated weekly for 12 weeks (cLD-shifts). Locomotor activity was monitored before the 4^th ventricle ChP and suprachiasmatic nuclei (SCN) explants were recorded in real time for PER2-driven population and single-cell bioluminescence rhythms. In addition, plasma immune marker concentrations and gene expression in ChP, prefrontal cortex, hippocampus and cerebellum were analyzed. cLL dampened the SCN clock but did not shorten the inactivity interval (sleep). cLD-shifts had no effect on the SCN clock, but transiently affected sleep duration and fragmentation. Both chronodisruption protocols dampened the ChP clock. Although immune markers were elevated in plasma and hippocampus, levels in ChP were unaffected, and unlike the liver clock, the ChP clock was resistant to lipopolysaccharide treatment. Importantly, both chronodisruption protocols reduced glucocorticoid signaling in ChP. The data demonstrate the high resistance of the ChP clock to inflammation, highlighting its role in protecting the brain from neuroinflammation, and on the other hand its high sensitivity to chronodisruption. Our results provide a novel link between human lifestyle-induced chronodisruption and the impairment of ChP-dependent brain homeostasis.

脑室中的脉络丛 (ChP) 对大脑稳态具有重要影响。在这项研究中，我们的目的是确定位于 ChP 的生物钟是否受到因与外部光/暗周期不一致和/或炎症引起的时间紊乱的影响。成年mPer2 ^Luc小鼠维持 LD12:12 周期或暴露于两种慢性时间紊乱模型之一 - 持续光照 22-25 周 (cLL) 或 LD12:12 周期的 6 小时相位提前，每周重复一次，持续 12 周（cLD-转变）。在实时记录^第四脑室 ChP 和视交叉上核 (SCN) 外植体之前监测运动活动，以了解 PER2 驱动的群体和单细胞生物发光节律。此外，还分析了 ChP、前额皮质、海马和小脑的血浆免疫标记物浓度和基因表达。 cLL 抑制了 SCN 时钟，但没有缩短不活动间隔（睡眠）。 cLD 变化对 SCN 时钟没有影响，但会短暂影响睡眠持续时间和碎片化。两种时间中断方案都会抑制 ChP 时钟。尽管血浆和海马中的免疫标记物升高，但 ChP 中的水平未受影响，并且与肝脏时钟不同，ChP 时钟对脂多糖治疗具有抵抗力。重要的是，两种时间中断方案均减少了 ChP 中的糖皮质激素信号传导。这些数据证明了 ChP 时钟对炎症的高度抵抗力，强调了它在保护大脑免受神经炎症影响方面的作用，另一方面它对时间紊乱的高度敏感性。我们的研究结果提供了人类生活方式引起的时间紊乱与 ChP 依赖性大脑稳态受损之间的新联系。