Počet záznamů: 1
Effects of Pregnanolone Glutamate and Its Metabolites on GABAA and NMDA Receptors and Zebrafish Behavior
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SYSNO ASEP 0572804 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Effects of Pregnanolone Glutamate and Its Metabolites on GABAA and NMDA Receptors and Zebrafish Behavior Tvůrce(i) Abramová, Vera (FGU-C)
Leal Alvarado, Vanessa (FGU-C) ORCID
Hill, M. (CZ)
Smejkalová, Tereza (FGU-C) RID, ORCID
Malý, Michal (FGU-C) ORCID
Valeš, Karel (FGU-C) RID, ORCID, SAI
Dittert, Ivan (FGU-C) ORCID
Božíková, Paulina (BTO-N)
Kysilov, Bohdan (FGU-C) ORCID, SAI
Hrčka Krausová, Barbora (FGU-C) ORCID, RID
Vyklický, Vojtěch (FGU-C) RID, ORCID, SAI
Balík, Aleš (FGU-C) RID, ORCID
Fili, Klevinda (FGU-C) ORCID
Kořínek, Miloslav (FGU-C) RID, ORCID
Chodounská, Hana (UOCHB-X) RID, ORCID
Kudová, Eva (UOCHB-X) RID, ORCID
Číž, D. (CZ)
Martinovič, J. (CZ)
Černý, Jiří (FGU-C) RID, ORCID
Bartůněk, Petr (UMG-J) RID
Vyklický ml., Ladislav (FGU-C) RID, ORCID, SAIZdroj.dok. ACS Chemical Neuroscience. - : American Chemical Society - ISSN 1948-7193
Roč. 14, č. 10 (2023), s. 1870-1883Poč.str. 14 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova negative allosteric modulator ; thigmotaxis ; steroid ; glutamate ; zebrafish Obor OECD Neurosciences (including psychophysiology CEP EF16_025/0007444 GA MZd - Ministerstvo zdravotnictví LM2023052 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy GA23-04922S GA ČR - Grantová agentura ČR TN02000109 GA TA ČR - Technologická agentura ČR Výzkumná infrastruktura CZ-OPENSCREEN IV - 90252 - Ústav molekulární genetiky AV ČR, v. v. i. Způsob publikování Omezený přístup Institucionální podpora FGU-C - RVO:67985823 ; BTO-N - RVO:86652036 ; UOCHB-X - RVO:61388963 ; UMG-J - RVO:68378050 UT WOS 000984445000001 EID SCOPUS 85159605177 DOI 10.1021/acschemneuro.3c00131 Anotace Multiple molecular targets have been identified to mediate membrane-delimited and nongenomic effects of natural and synthetic steroids, but the influence of steroid metabolism on neuroactive steroid signaling is not well understood. To begin to address this question, we set out to identify major metabolites of a neuroprotective synthetic steroid 20-oxo5 beta-pregnan-3 alpha-yl L-glutamyl 1-ester (pregnanolone glutamate, PAG) and characterize their effects on GABAA and NMDA receptors (GABARs, NMDARs) and their influence on zebrafish behavior. Gas chromatography- mass spectrometry was used to assess concentrations of PAG and its metabolites in the hippocampal tissue of juvenile rats following intraperitoneal PAG injection. PAG is metabolized in the peripheral organs and nervous tissue to 20-oxo-17 alpha-hydroxy-5 beta-pregnan-3 alpha-yl L-glutamyl 1-ester (17-hydroxypregnanolone glutamate, 17-OH-PAG), 3 alpha-hydroxy-5 beta-pregnan-20-one (pregnanolone, PA), and 3 alpha,17 alpha-dihydroxy-5 beta-pregnan-20-one (17-hydroxypregnanolone, 17-OH-PA). Patch-clamp electrophysiology experiments in cultured hippocampal neurons demonstrate that PA and 17-OH-PA are potent positive modulators of GABARs, while PAG and 17-OH-PA have a moderate inhibitory effect at NMDARs. PAG, 17-OH-PA, and PA diminished the locomotor activity of zebrafish larvae in a dose-dependent manner. Our results show that PAG and its metabolites are potent modulators of neurotransmitter receptors with behavioral consequences and indicate that neurosteroid-based ligands may have therapeutic potential. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2024 Elektronická adresa https://doi.org/10.1021/acschemneuro.3c00131
Počet záznamů: 1