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The CSF secretion rate is elevated in the dark phase in both humans and rats, which could support the CSF flow along the paravascular spaces that may be implicated in waste clearance. The similar diurnal CSF dynamics pattern observed in the day-active human and the nocturnal rat suggests a circadian regulation of this physiological variable, rather than sleep itself. To obtain a catalog of potential molecular drivers that could provide the day\u2013night-associated modulation of the CSF secretion rate, we determined the diurnal fluctuation in the rat choroid plexus transcriptomic profile with RNA-seq and in the CSF metabolomics with ultraperformance liquid chromatography combined with mass spectrometry. We detected significant fluctuation of 19 CSF metabolites and differential expression of 2,778 choroid plexus genes between the light and the dark phase, the latter of which encompassed circadian rhythm\u2013related genes and several choroid plexus transport mechanisms. The fluctuating components were organized with joint pathway analysis, of which several pathways demonstrated diurnal regulation. Our results illustrate substantial transcriptional and metabolic light\u2013dark phase\u2013mediated changes taking place in the rat choroid plexus and its encircling CSF. The combined data provide directions toward future identification of the molecular pathways governing the fluctuation of this physiological process and could potentially be harnessed to modulate the CSF dynamics in pathology.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgad262","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T05:38:39Z","timestamp":1691645919000},"source":"Crossref","is-referenced-by-count":21,"title":["Day\u2013night fluctuations in choroid plexus transcriptomics and cerebrospinal fluid metabolomics"],"prefix":"10.1093","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2294-1859","authenticated-orcid":false,"given":"Beatriche Louise","family":"Edelbo","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Copenhagen , 2200 Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren 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