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Glucocorticoids reset circadian clock in choroid plexus via period genes

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, ORCID}
Source Title	Journal of Endocrinology. - : BioScientifica - ISSN 0022-0795 Roč. 248, č. 2 (2021), s. 155-166
Number 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	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

Number of the records: 1