Preferential Inhibition of Tonically over Phasically Activated NMDA Receptors by Pregnane Derivatives

Vyklický, Vojtěch; Smejkalová, Tereza; Krausová, Barbora; Balík, Aleš; Kořínek, Miloslav; Borovská, Jiřina; Horák, Martin; Chvojková, Markéta; Kletečková, Lenka; Valeš, Karel; Černý, Jiří; Nekardová, Michaela; Chodounská, Hana; Kudová, Eva; Vyklický ml., Ladislav

doi:https://dx.doi.org/10.1523/JNEUROSCI.3181-15.2016

Počet záznamů: 1

Preferential Inhibition of Tonically over Phasically Activated NMDA Receptors by Pregnane Derivatives

1.

SYSNO ASEP	0459355
Druh ASEP	J - Článek v odborném periodiku
Zařazení RIV	J - Článek v odborném periodiku
Poddruh J	Článek ve WOS
Název	Preferential Inhibition of Tonically over Phasically Activated NMDA Receptors by Pregnane Derivatives
Tvůrce(i)	Vyklický, Vojtěch (FGU-C)_{RID, ORCID, SAI} Smejkalová, Tereza (FGU-C)_{RID, ORCID} Krausová, Barbora (FGU-C)_ORCID Balík, Aleš (FGU-C)_{RID, ORCID} Kořínek, Miloslav (FGU-C)_{RID, ORCID} Borovská, Jiřina (FGU-C) Horák, Martin (FGU-C)_{RID, ORCID} Chvojková, Markéta (FGU-C)_{RID, ORCID} Kletečková, Lenka (FGU-C)_ORCID Valeš, Karel (FGU-C)_{RID, ORCID, SAI} Černý, Jiří (FGU-C)_{RID, ORCID} Nekardová, Michaela (UOCHB-X)_RID Chodounská, Hana (UOCHB-X)_{RID, ORCID} Kudová, Eva (UOCHB-X)_{RID, ORCID} Vyklický ml., Ladislav (FGU-C)_{RID, ORCID, SAI}
Zdroj.dok.	Journal of Neuroscience. - : Society for Neuroscience - ISSN 0270-6474 Roč. 36, č. 7 (2016), s. 2161-2175
Poč.str.	15 s.
Jazyk dok.	eng - angličtina
Země vyd.	US - Spojené státy americké
Klíč. slova	memantine ; neuroprotection ; neurosteroid ; NMDA receptor ; pregnanolone sulfate ; synaptic transmission
Vědní obor RIV	ED - Fyziologie
CEP	GAP303/12/1464 GA ČR - Grantová agentura ČR
	GBP304/12/G069 GA ČR - Grantová agentura ČR
	TE01020028 GA TA ČR - Technologická agentura ČR
	GBP208/12/G016 GA ČR - Grantová agentura ČR
	EE2.3.30.0025 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy
	ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy
Institucionální podpora	FGU-C - RVO:67985823 ; UOCHB-X - RVO:61388963
UT WOS	000370818700009
EID SCOPUS	84958817737
DOI	10.1523/JNEUROSCI.3181-15.2016
Anotace	Postsynaptic N-methyl-D-aspartate receptors (NMDARs) phasically activated by presynaptically released glutamate are critical for synaptic transmission and plasticity. However, under pathological conditions, excessive activation of NMDARs by tonically increased ambient glutamate contributes to excitotoxicity associated with various acute and chronic neurological disorders. Here, using heterologously expressed GluN1/GluN2A and GluN1/GluN2B receptors and rat autaptic hippocampal microisland cultures, we show that pregnanolone sulfate inhibits NMDAR currents induced by a prolonged glutamate application with a higher potency than the NMDAR component of EPSCs. For synthetic pregnanolone derivatives substituted with a carboxylic acid moiety at the end of an aliphatic chain of varying length and attached to the steroid skeleton at C3, the difference in potency between tonic and phasic inhibition increased with the length of the residue. The steroid with the longest substituent, pregnanolone hemipimelate, had no effect on phasically activated receptors while inhibiting tonically activated receptors. In behavioral tests, pregnanolone hemipimelate showed neuroprotective activity without psychomimetic symptoms. These results provide insight into the influence of steroids on neuronal function and stress their potential use in the development of novel therapeutics with neuroprotective action.
Pracoviště	Fyziologický ústav
Kontakt	Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400
Rok sběru	2017

Počet záznamů: 1