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Extra-synaptic GABA...
Extra-synaptic GABAA receptor potentiation and neurosteroid-induced learning deficits are inhibited by GR3027, a GABAA modulating steroid antagonist
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- Bengtsson, Sara K. S., 1978- (författare)
- Umeå universitet,Obstetrik och gynekologi
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- Sjöstedt, Jessica (författare)
- Umeå universitet,Obstetrik och gynekologi
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- Malinina, Evgenya (författare)
- Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB),Obstetrik och gynekologi
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- Das, Roshni (författare)
- Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB),Umecrine Cognition AB, Solna, Sweden
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- Doverskog, Magnus (författare)
- Umecrine Cognition AB, Solna, Sweden
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- Johansson, Inga-Maj (författare)
- Umeå universitet,Obstetrik och gynekologi,Umecrine Cognition AB, Solna, Sweden
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- Haage, David (författare)
- Mittuniversitetet,Umeå universitet,Obstetrik och gynekologi,Department of Nursing Sciences, Mid Sweden University, Sundsvall, Sweden,Institutionen för hälsovetenskaper (HOV)
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- Bäckström, Torbjörn (författare)
- Umeå universitet,Obstetrik och gynekologi,Umecrine Cognition AB, Solna, Sweden
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(creator_code:org_t)
- MDPI, 2023
- 2023
- Engelska.
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 13:10
- Relaterad länk:
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https://doi.org/10.3...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.3...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- 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)
Nyckelord
- allopregnanolone
- GABAA receptor
- GR3027 improves memory
- memory impairment
- THDOC
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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