GABAA receptor modulating steroid antagonists (GAMSA) are functional in vivo.
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TLDR
It is shown that pharmacological treatment with allopregnanolone can promote neurogenesis and positively influence learning and memory of trace eye-blink conditioning in mice and that 3β-hydroxy-steroids antagonize this positive neurosteroid-mediated modulation of the GABAA receptor.About:
This article is published in The Journal of Steroid Biochemistry and Molecular Biology.The article was published on 2016-06-01 and is currently open access. It has received 29 citations till now. The article focuses on the topics: Allopregnanolone & Tetrahydrodeoxycorticosterone.read more
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Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy.
Christopher F. Rose,Piero Amodio,Jasmohan S. Bajaj,Radha K. Dhiman,Sara Montagnese,Simon D. Taylor-Robinson,Hendrik Vilstrup,Rajiv Jalan +7 more
TL;DR: This review will critically discuss the latest classification of HE, as well as the pathogenesis and pathophysiological pathways underlying the neurological decline in patients with end-stage liver disease.
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Important Unresolved Questions in the Management of Hepatic Encephalopathy: An ISHEN Consensus
Jasmohan S. Bajaj,Mette Munk Lauridsen,Elliot B. Tapper,Andres Duarte-Rojo,Robert S. Rahimi,Puneeta Tandon,Debbie L. Shawcross,Dominique Thabut,Radha K. Dhiman,Manuel Romero-Gómez,Barjesh Chander Sharma,Sara Montagnese +11 more
TL;DR: Members of the International Society for Hepatic Encephalopathy and Nitrogen Metabolism recognized 5 key unresolved questions in HE management, and a consensus document addresses these topical issues with a succinct review of the literature and statements that critically evaluate the current science and practice.
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Differential effects of the 18-kDa translocator protein (TSPO) ligand etifoxine on steroidogenesis in rat brain, plasma and steroidogenic glands: Pharmacodynamic studies.
TL;DR: It is suggested that adrenal steroids upregulated by etifoxine make an important contribution to the steroids present in brain, and this work provides a precise and complete view of steroids regulated by et ifoxine that could be useful in therapeutic research.
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A pilot study of golexanolone, a new GABA-A receptor-modulating steroid antagonist, in patients with covert hepatic encephalopathy.
Sara Montagnese,Mette Munk Lauridsen,Hendrik Vilstrup,Lisa Zarantonello,Geza Lakner,Sergey Fitilev,Igor A. Zupanets,Irina Kozlova,Elena Bunkova,Krzysztof Tomasiewicz,Jan Erik Berglund,Fredrik Rorsman,Hannes Hagström,Stergios Kechagias,Carin Edmark Ocklind,Joe Mauney,Fredrik Thunarf,Masoud Mokhatarani,Torbjörn Bäckström,Magnus Doverskog,Lars-Erik Lins,Maria Månsson,Per Samuelson,Dag Nilsson,Martin Schalling,Maja Johansson,Eva Arlander,Bruce F. Scharschmidt +27 more
TL;DR: Golexanolone as mentioned in this paper is a small molecule GABA-A receptor modulating steroid antagonist under development for treatment of cognitive and vigilance disorders due to allosteric over-activation of GABA receptors by neurosteroids.
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Stigmasterol can be new steroidal drug for neurological disorders: Evidence of the GABAergic mechanism via receptor modulation.
TL;DR: In this paper, the effects of stigmasterol, a plant sterol (phytosterol) isolated from Artemisia indica Linn on neurological disorders, were investigated on various recombinant GABAA receptor subtypes expressed in Xenopus laevis oocytes.
References
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Brief but Chronic Increase in Allopregnanolone Cause Accelerated AD Pathology Differently in Two Mouse Models
TL;DR: One month of chronic treatment with elevated ALLO levels within physiological range impaired learning and memory function in the Swe/Arc female and male mice, and both Swe/ Arc and Swe/PS1 mice showed signs of accelerated disease progression.
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Increased neurosteroid sensitivity – An explanation to symptoms associated with chronic work related stress in women?
TL;DR: It is hypothesized that the α4 and delta subunits are up-regulated elevating the responsiveness to allopregnanolone and change the effect of flumazenil, which provides a potential explanation to the burnout syndrome.
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Progesterone and its metabolites as therapeutic targets in psychiatric disorders
Giovana Bristot,Bruna Maria Ascoli,Carolina Gubert,Bruna Panizzutti,Flávio Kapczinski,Adriane R. Rosa +5 more
TL;DR: Both preclinical and clinical studies show that certain treatments may normalize the levels of PROG, suggesting that the amelioration of psychiatric symptoms may occur due to upregulation of PROG metabolites, giving support to new possibilities of treatment for patients with psychiatric symptoms.
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Ammonia inhibits long-term potentiation via neurosteroid synthesis in hippocampal pyramidal neurons
TL;DR: Results indicate that GABA-enhancing neurosteroids, synthesized locally within pyramidal neurons, contribute significantly to ammonia-mediated synaptic dysfunction and suggest that the manipulation of neurosteroid synthesis could provide a strategy to improve cognitive function in individuals with hyperammonemia.
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Finasteride improves motor, EEG, and cellular changes in rat brain in thioacetamide-induced hepatic encephalopathy.
Dušan Mladenović,Dragan Hrnčić,Nataša Petronijević,Gordana Jevtić,Tatjana Radosavljević,Aleksandra Rašić-Marković,Nela Puškaš,Nebojša Maksić,Olivera Stanojlović +8 more
TL;DR: Finasteride improves motor and EEG changes in TAA-induced HE and completely prevents the development of hepatic coma.