Extra-synaptic GABAA receptor potentiation and neurosteroid-induced learning deficits are inhibited by GR3027, a GABAA modulating steroid antagonist

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Search: WFRF:(Bäckström Torbjörn) > (2020-2024) > Extra-synaptic GABA...

Details
MARC

Bengtsson, Sara K. S.,1978-Umeå universitet,Obstetrik och gynekologi (author)

Extra-synaptic GABAA receptor potentiation and neurosteroid-induced learning deficits are inhibited by GR3027, a GABAA modulating steroid antagonist

Article/chapterEnglish2023

Publisher, publication year, extent ...

MDPI,2023
electronicrdacarrier

Numbers

LIBRIS-ID:oai:DiVA.org:umu-216186
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-216186URI
https://doi.org/10.3390/biom13101496DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-49794URI

Supplementary language notes

Language:English
Summary in:English

Part of subdatabase

SwePubSwePub

Classification

Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

Objectives In Vitro: To study the effects of GR3027 (golexanolone) on neurosteroid-induced GABA-mediated current responses under physiological GABAergic conditions with recombinant human α5β3γ2L and α1β2γ2L GABAA receptors expressed in human embryonic kidney cells, using the response patch clamp technique combined with the Dynaflow™ application system. With α5β3γ2L receptors, 0.01–3 μM GR3027, in a concentration-dependent manner, reduced the current response induced by 200 nM THDOC + 0.3 µM GABA, as well as the THDOC-induced direct gated effect. GR3027 (1 μM) alone had no effect on the GABA-mediated current response or current in the absence of GABA. With α1β2γ2L receptors, GR3027 alone had no effect on the GABA-mediated current response or did not affect the receptor by itself. Meanwhile, 1–3 µM GR3027 reduced the current response induced by 200 nM THDOC + 30 µM GABA and 3 µM GR3027 that induced by 200 nM THDOC when GABA was not present. Objectives In Vivo: GR3027 reduces allopregnanolone (AP)-induced decreased learning and anesthesia in male Wistar rats. Rats treated i.v. with AP (2.2 mg/kg) or vehicle were given GR3027 in ratios of 1:0.5 to 1:5 dissolved in 10% 2-hydroxypropyl-beta-cyclodextrin. A dose ratio of AP:GR3027 of at least 1:2.5 antagonized the AP-induced decreased learning in the Morris Water Mase (MWM) and 1:7.5 antagonized the loss of righting reflex (LoR). GR3027 treatment did not change other functions in the rat compared to the vehicle group. Conclusions: GR3027 functions in vitro as an inhibitor of GABAA receptors holding α5β3γ2L and α1β2γ2L, in vivo, in the rat, as a dose-dependent inhibitor toward AP’s negative effects on LoR and learning in the MWM.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Fysiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Physiology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Urologi och njurmedicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Urology and Nephrology hsv//eng
allopregnanolone
GABAA receptor
GR3027 improves memory
memory impairment
THDOC

Added entries (persons, corporate bodies, meetings, titles ...)

Sjöstedt, JessicaUmeå universitet,Obstetrik och gynekologi (author)
Malinina, EvgenyaUmeå universitet,Institutionen för integrativ medicinsk biologi (IMB),Obstetrik och gynekologi(Swepub:umu)evma0003 (author)
Das, RoshniUmeå universitet,Institutionen för integrativ medicinsk biologi (IMB),Umecrine Cognition AB, Solna, Sweden(Swepub:umu)roda0034 (author)
Doverskog, MagnusUmecrine Cognition AB, Solna, Sweden (author)
Johansson, Inga-MajUmeå universitet,Obstetrik och gynekologi,Umecrine Cognition AB, Solna, Sweden(Swepub:umu)injo0002 (author)
Haage, DavidMittuniversitetet,Umeå universitet,Obstetrik och gynekologi,Department of Nursing Sciences, Mid Sweden University, Sundsvall, Sweden,Institutionen för hälsovetenskaper (HOV)(Swepub:miun)davhag (author)
Bäckström, TorbjörnUmeå universitet,Obstetrik och gynekologi,Umecrine Cognition AB, Solna, Sweden(Swepub:umu)toba0001 (author)
Umeå universitetObstetrik och gynekologi (creator_code:org_t)

Related titles

In:Biomolecules: MDPI13:102218-273X

Internet link

Find in a library

Biomolecules (Search for host publication in LIBRIS)

To the university's database

Find more in SwePub

By the author/editor: Bengtsson, Sara ...; Sjöstedt, Jessic ...; Malinina, Evgeny ...; Das, Roshni; Doverskog, Magnu ...; Johansson, Inga- ...; show more...; Haage, David; Bäckström, Torbj ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Physiology

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Urology and Neph ...

Articles in the publication: Biomolecules

By the university: Umeå University; Mid Sweden University

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se