Choroid plexus (ChP), the brain structure primarily responsible for cerebrospinal fluid production, contains a robust circadian clock with unknown function. We used genetic mouse models (WT, mPer2Luc, ChP-specific Bmal1 knockout) combined with surgical lesion of the SCN (SCNx), time-resolved transcriptomics, and single cell luminescence microscopy. We found that the ChP clock regulates cerebrospinal fluid circadian secretome, precisely times endoplasmic reticulum stress response, and controls genes involved in neurodegenerative diseases. In ChP of SCNx mice, the rhythms were severely dampened to a comparable extent as in mice with ChP-specific Bmal1 knockout; they were restored by daily injections of dexamethasone. Our data demonstrate that the ChP clock controls tissue-specific gene expression and is strongly dependent on the presence of a functional connection with the SCN. The results may contribute to the search for a novel link between ChP clock disruption and impaired brain health.

Fig: A. Workflow. B. Period of locomotor activity in Control and SCNx mice. C. SCN after sham surgery and after lesion. D. Rhythms in SCNx ChP are dampened to similar extent as rhythms in ChP from tissues-specific Bmal1-KO. E. Rhythmic genes in Control (left) or SCNx (right) ChP samples. F. Phase histogram of genes Control (left) or SCNx (right) ChP samples. G. PER2::LUCIFERASE rhythms in single-cell sized ROIs across an explanted ChP from either Control or SCNx mice.