Circadian clock in choroid plexus is resistant to immune challenge but dampens in response to chronodisruption

0583226 - FGÚ 2025 RIV NL eng J - Journal Article
Drapšin, Milica - Dočkal, Tereza - Houdek, Pavel - Sládek, Martin - Semenovykh, Kateryna - Sumová, Alena
Circadian clock in choroid plexus is resistant to immune challenge but dampens in response to chronodisruption.
Brain Behavior and Immunity. Roč. 117, March (2024), s. 255-269. ISSN 0889-1591. E-ISSN 1090-2139
R&D Projects: GA ČR(CZ) GA21-09745S
Institutional support: RVO:67985823
Keywords : choroid plexus * chronodisruption * circadian clock * constant light * bioluminescence rhythm * neuroinflammation * sleep disruption * mPer2Luc mouse
OECD category: Neurosciences (including psychophysiology
Impact factor: 15.1, year: 2022
https://doi.org/10.1016/j.bbi.2024.01.217

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 mPer2Luc 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 4th 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.
Permanent Link: https://hdl.handle.net/11104/0351229