FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2148412570> ?p ?o ?g. }

• W2148412570 endingPage "1041" @default.
• W2148412570 startingPage "1031" @default.
• W2148412570 abstract "Testosterone modulates seizure susceptibility, but the underlying mechanisms are obscure. Recently, we demonstrated that testosterone affects seizure activity via its conversion to neurosteroids in the brain. Androstanediol (5alpha-androstan-3alpha,17beta-diol) is an endogenous neurosteroid synthesized from testosterone. However, the molecular mechanism underlying the seizure protection activity of androstanediol remains unclear. Here, we show that androstanediol has positive allosteric activity as a GABA(A) receptor modulator. In whole-cell recordings from acutely dissociated hippocampus CA1 pyramidal cells, androstanediol (but not its 3beta-epimer) produced a concentration-dependent enhancement of GABA-activated currents (EC(50) of 5 microM). At 1 microM, androstanediol produced a 50% potentiation of GABA responses. In the absence of GABA, androstanediol has moderate direct effects on GABA(A) receptor-mediated currents at high concentrations. Systemic doses of androstanediol (5-100 mg/kg), but not its 3beta-epimer, caused dose-dependent suppression of behavioral and electrographic seizures in mouse hippocampus kindling, which is a model of temporal lobe epilepsy. The ED(50) value for antiseizure effects of androstanediol was 50 mg/kg, which did not produce sedation/motor toxicity. At high (2x ED(50)) doses, androstanediol produced complete seizure protection that lasted for up to 3 h after injection. The estimated plasma concentrations of androstanediol producing 50% seizure protection in the kindling model (10.6 microM) are within the range of concentrations that modulate GABA(A) receptors. These studies suggest that androstanediol could be a neurosteroid mediator of testosterone actions on neuronal excitability and seizure susceptibility via its activity as a GABA(A) receptor modulator and that androstanediol may play a key role in men with epilepsy, especially during the age-related decline in androgen levels." @default.
• W2148412570 created "2016-06-24" @default.
• W2148412570 creator A5002821906 @default.
• W2148412570 creator A5011714801 @default.
• W2148412570 date "2010-06-15" @default.
• W2148412570 modified "2023-10-16" @default.
• W2148412570 title "The Testosterone-Derived Neurosteroid Androstanediol Is a Positive Allosteric Modulator of GABA_A Receptors" @default.
• W2148412570 cites W1647312149 @default.
• W2148412570 cites W1966722313 @default.
• W2148412570 cites W1976707885 @default.
• W2148412570 cites W1983342728 @default.
• W2148412570 cites W1984625181 @default.
• W2148412570 cites W1984824362 @default.
• W2148412570 cites W1998236920 @default.
• W2148412570 cites W1998765262 @default.
• W2148412570 cites W2008079372 @default.
• W2148412570 cites W2016140176 @default.
• W2148412570 cites W2017227716 @default.
• W2148412570 cites W2017690593 @default.
• W2148412570 cites W2020886601 @default.
• W2148412570 cites W2022549781 @default.
• W2148412570 cites W2024344189 @default.
• W2148412570 cites W2024498506 @default.
• W2148412570 cites W2025645923 @default.
• W2148412570 cites W2027537591 @default.
• W2148412570 cites W2030295462 @default.
• W2148412570 cites W2031193882 @default.
• W2148412570 cites W2032508898 @default.
• W2148412570 cites W2033837647 @default.
• W2148412570 cites W2053715516 @default.
• W2148412570 cites W2056072690 @default.
• W2148412570 cites W2071797393 @default.
• W2148412570 cites W2072900447 @default.
• W2148412570 cites W2077468380 @default.
• W2148412570 cites W2083418663 @default.
• W2148412570 cites W2083447043 @default.
• W2148412570 cites W2091060078 @default.
• W2148412570 cites W2103946141 @default.
• W2148412570 cites W2111671651 @default.
• W2148412570 cites W2127146014 @default.
• W2148412570 cites W2130287184 @default.
• W2148412570 cites W2148377354 @default.
• W2148412570 cites W2165699104 @default.
• W2148412570 doi "https://doi.org/10.1124/jpet.110.169854" @default.
• W2148412570 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2939675" @default.
• W2148412570 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20551294" @default.
• W2148412570 hasPublicationYear "2010" @default.
• W2148412570 type Work @default.
• W2148412570 sameAs 2148412570 @default.
• W2148412570 citedByCount "143" @default.
• W2148412570 countsByYear W21484125702012 @default.
• W2148412570 countsByYear W21484125702013 @default.
• W2148412570 countsByYear W21484125702014 @default.
• W2148412570 countsByYear W21484125702015 @default.
• W2148412570 countsByYear W21484125702016 @default.
• W2148412570 countsByYear W21484125702017 @default.
• W2148412570 countsByYear W21484125702018 @default.
• W2148412570 countsByYear W21484125702019 @default.
• W2148412570 countsByYear W21484125702020 @default.
• W2148412570 countsByYear W21484125702021 @default.
• W2148412570 countsByYear W21484125702022 @default.
• W2148412570 countsByYear W21484125702023 @default.
• W2148412570 crossrefType "journal-article" @default.
• W2148412570 hasAuthorship W2148412570A5002821906 @default.
• W2148412570 hasAuthorship W2148412570A5011714801 @default.
• W2148412570 hasBestOaLocation W21484125702 @default.
• W2148412570 hasConcept C100691959 @default.
• W2148412570 hasConcept C126322002 @default.
• W2148412570 hasConcept C134018914 @default.
• W2148412570 hasConcept C166342909 @default.
• W2148412570 hasConcept C168258287 @default.
• W2148412570 hasConcept C170493617 @default.
• W2148412570 hasConcept C185592680 @default.
• W2148412570 hasConcept C24998067 @default.
• W2148412570 hasConcept C2776038425 @default.
• W2148412570 hasConcept C2776801781 @default.
• W2148412570 hasConcept C2778938600 @default.
• W2148412570 hasConcept C2779279991 @default.
• W2148412570 hasConcept C44796713 @default.
• W2148412570 hasConcept C55493867 @default.
• W2148412570 hasConcept C71924100 @default.
• W2148412570 hasConcept C86803240 @default.
• W2148412570 hasConcept C98274493 @default.
• W2148412570 hasConceptScore W2148412570C100691959 @default.
• W2148412570 hasConceptScore W2148412570C126322002 @default.
• W2148412570 hasConceptScore W2148412570C134018914 @default.
• W2148412570 hasConceptScore W2148412570C166342909 @default.
• W2148412570 hasConceptScore W2148412570C168258287 @default.
• W2148412570 hasConceptScore W2148412570C170493617 @default.
• W2148412570 hasConceptScore W2148412570C185592680 @default.
• W2148412570 hasConceptScore W2148412570C24998067 @default.
• W2148412570 hasConceptScore W2148412570C2776038425 @default.
• W2148412570 hasConceptScore W2148412570C2776801781 @default.
• W2148412570 hasConceptScore W2148412570C2778938600 @default.
• W2148412570 hasConceptScore W2148412570C2779279991 @default.
• W2148412570 hasConceptScore W2148412570C44796713 @default.
• W2148412570 hasConceptScore W2148412570C55493867 @default.
• W2148412570 hasConceptScore W2148412570C71924100 @default.

• next