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Glucocorticoids reset circadian clock in choroid plexus via period genes
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SYSNO ASEP 0541621 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Glucocorticoids reset circadian clock in choroid plexus via period genes Author(s) Liška, Karolína (FGU-C) ORCID
Sládek, Martin (FGU-C) RID, ORCID, SAI
Čečmanová, Vendula (FGU-C)
Sumová, Alena (FGU-C) RID, ORCIDSource Title Journal of Endocrinology. - : BioScientifica - ISSN 0022-0795
Roč. 248, č. 2 (2021), s. 155-166Number of pages 12 s. Language eng - English Country GB - United Kingdom Keywords choroid plexus ; circadian clock ; glucocorticoids ; dexamethasone ; circadian entrainment ; phase-response curve Subject RIV ED - Physiology OECD category Physiology (including cytology) R&D Projects LM2015062 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GBP304/12/G069 GA ČR - Czech Science Foundation (CSF) Method of publishing Open access with time embargo (01.02.2022) Institutional support FGU-C - RVO:67985823 UT WOS 000629252300010 EID SCOPUS 85102602029 DOI https://doi.org/10.1530/JOE-20-0526 Annotation The epithelial cells of choroid plexus (CP) in brain ventricles produce cerebrospinal fluid and act as the blood-cerebrospinal fluid barrier. In this study, we confirmed that CP in the 4th ventricle is composed of cellular oscillators that all harbor glucocorticoid receptors and are mutually synchronized to produce a robust clock gene expression rhythm detectable at the tissue level in vivo and in vitro. Animals lacking glucocorticoids (GCs) due to surgical removal of adrenal glands had Per1, Per2, Nr1d1 and Bmal1 clock gene rhythmicity in their CP significantly dampened, whereas subjecting them to daily bouts of synthetic GC analog, dexamethasone (DEX), reinforced those rhythms. We verified these in vivo effects using an in vitro model of organotypic CP explants, depending on the time of its application, DEX significantly increased the amplitude and efficiently reset the phase of the CP clock. The results are the first description of a PRC for a non-neuronal clock in the brain, demonstrating that CP clock shares some properties with the non-neuronal clocks elsewhere in the body. Finally, we found that DEX exhibited multiple synergic effects on the CP clock, including acute activation of Per1 expression and change of PER2 protein turnover rate. The DEX-induced shifts of the CP clock were partially mediated via PKA-ERK1/2 pathway. The results provide the first evidence that the GC rhythm strengthens and entrains the clock in the CP helping thus fine-tune the brain environment according to time of day. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2022 Electronic address https://doi.org/10.1530/JOE-20-0526
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