Počet záznamů: 1
High Sensitivity of the Circadian Clock in the Hippocampal Dentate Gyrus to Glucocorticoid- and GSK3-Beta-Dependent Signals
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SYSNO ASEP 0557003 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název High Sensitivity of the Circadian Clock in the Hippocampal Dentate Gyrus to Glucocorticoid- and GSK3-Beta-Dependent Signals Tvůrce(i) Liška, Karolína (FGU-C) ORCID
Sládek, Martin (FGU-C) RID, ORCID, SAI
Houdek, Pavel (FGU-C) ORCID
Shrestha, N. (CA)
Lužná, Vendula (FGU-C)
Ralph, M. R. (CA)
Sumová, Alena (FGU-C) RID, ORCIDZdroj.dok. Neuroendocrinology. - : Karger - ISSN 0028-3835
Roč. 112, č. 4 (2022), s. 384-398Poč.str. 15 s. Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova adrenalectomy ; circadian clock ; dexamethasone ; glucocorticoids ; GSK3-beta ; hippocampus Obor OECD Physiology (including cytology) CEP LM2015062 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy GA21-09745S GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 UT WOS 000699977300001 EID SCOPUS 85127358087 DOI 10.1159/000517689 Anotace Aims: Circadian clocks in the hippocampus (HPC) align memory processing with appropriate time of day. Our study was aimed at ascertaining the specificity of glycogen synthase kinase 3-beta (GSK3 beta)- and glucocorticoid (GC)-dependent pathways in the entrainment of clocks in individual HPC regions, CA1-3, and dentate gyrus (DG). Methods: The role of GCs was addressed in vivo by comparing the effects of adrenalectomy (ADX) and subsequent dexamethasone (DEX) supplementation on clock gene expression profiles (Per1, Per2, Nr1d1, and Bmal1). In vitro the effects of DEX and the GSK3 beta inhibitor, CHIR-99021, were assessed from recordings of bioluminescence rhythms in HPC organotypic explants of mPER2(Luc) mice. Results: Circadian rhythms of clock gene expression in all HPC regions were abolished by ADX, and DEX injections to the rats rescued those rhythms in DG. The DEX treatment of the HPC explants significantly lengthened periods of the bioluminescence rhythms in all HPC regions with the most significant effect in DG. In contrast to DEX, CHIR-99021 significantly shortened the period of bioluminescence rhythm. Again, the effect was most significant in DG which lacks the endogenously inactivated (phosphorylated) form of GSK3 beta. Co-treatment of the explants with CHIR-99021 and DEX produced the CHIR-99021 response. Therefore, the GSK3 beta-mediated pathway had dominant effect on the clocks. Conclusion: GSK3 beta- and GC-dependent pathways entrain the clock in individual HPC regions by modulating their periods in an opposite manner. The results provide novel insights into the mechanisms connecting the arousal state-relevant signals with temporal control of HPC-dependent memory and cognitive functions. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2023 Elektronická adresa https://doi.org/10.1159/000517689
Počet záznamů: 1