Neuroactive Steroids Reverse Tonic Inhibitory Deficits in Fragile X Syndrome Mouse Model.

Frontiers in Molecular Neuroscience
Amit ModgilPaul A Davies

Abstract

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. A reduction in neuronal inhibition mediated by γ-aminobutyric acid type A receptors (GABAARs) has been implicated in the pathophysiology of FXS. Neuroactive steroids (NASs) are known allosteric modulators of GABAAR channel function, but recent studies from our laboratory have revealed that NASs also exert persistent metabotropic effects on the efficacy of tonic inhibition by increasing the protein kinase C (PKC)-mediated phosphorylation of the α4 and β3 subunits which increase the membrane expression and boosts tonic inhibition. We have assessed the GABAergic signaling in the hippocampus of fragile X mental retardation protein (FMRP) knock-out (Fmr1 KO) mouse. The GABAergic tonic current in dentate gyrus granule cells (DGGCs) from 3- to 5-week-old (p21-35) Fmr1 KO mice was significantly reduced compared to WT mice. Additionally, spontaneous inhibitory post synaptic inhibitory current (sIPSC) amplitudes were increased in DGGCs from Fmr1 KO mice. While sIPSCs decay in both genotypes was prolonged by the prototypic benzodiazepine diazepam, those in Frm1-KO mice were selectively potentiated by RO15-4513. Consistent with this altered pharmacology,...Continue Reading

References

Feb 1, 1990·Journal of Neurology·S A MusumeciP Bergonzi
Mar 12, 1998·Brain Research. Molecular Brain Research·N J Leidenheimer, R Chapell
Aug 17, 1999·Epilepsia·S A MusumeciM Elia
Apr 27, 2002·Journal of Neurophysiology·Zoltan Nusser, Istvan Mody
Jan 16, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jasmina N JovanovicStephen J Moss
Apr 28, 2004·Trends in Neurosciences·Alexey SemyanovR Angus Silver
Aug 26, 2006·European Child & Adolescent Psychiatry·Roberto Canitano
Oct 19, 2006·Brain Research·Charlotte D'HulstR Frank Kooy
Feb 27, 2007·Brain & Development·Hitoshi Hara
May 26, 2007·The Journal of Physiology·Joseph Glykys, Istvan Mody
Nov 16, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Chengsan SunJaideep Kapur
Dec 28, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Usha NarayananStephen T Warren
Sep 13, 2008·Cerebral Cortex·Giulia CuriaMassimo Avoli
Sep 30, 2008·Journal of Autism and Developmental Disorders·S Hossein FatemiPaul D Thuras
Nov 14, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Doo-Sup ChoiRobert O Messing
Oct 16, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Delia BelelliDavid W Cope
Nov 26, 2009·Molecular Psychiatry·R J DelahantyJ S Sutcliffe
Dec 4, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ivan PavlovMatthew C Walker
Jan 13, 2010·Journal of Autism and Developmental Disorders·S Hossein FatemiPaul D Thuras
Jul 31, 2010·Autism : the International Journal of Research and Practice·Sophie E Lind
Oct 14, 2010·The Journal of Biological Chemistry·Armen M AbramianStephen J Moss
Aug 10, 2011·Neural Plasticity·Jocelyn J LeBlanc, Michela Fagiolini
Oct 20, 2011·Results and Problems in Cell Differentiation·Michael R Tranfaglia
May 1, 2012·Trends in Neurosciences·Rhiannon M MeredithIoannis Kramvis
May 5, 2012·Journal of Autism and Developmental Disorders·Jing-Qiong Kang, Gregory Barnes
Nov 28, 2012·Biological Psychology·Melle J W Van der Molen, Maurits W Van der Molen
Apr 19, 2013·Nature Reviews. Neuroscience·Ethan M Goldberg, Douglas A Coulter
Apr 26, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Karla KretschmannovaPaul A Davies
Jun 4, 2013·Nature Neuroscience·J Tiago GonçalvesCarlos Portera-Cailliau
Feb 13, 2014·Nature Communications·L M RangelL K Quinn
Apr 30, 2014·Proceedings of the National Academy of Sciences of the United States of America·Armen M AbramianStephen J Moss
Oct 7, 2014·Frontiers in Cellular Neuroscience·Rainer Rupprecht
May 1, 2015·American Journal on Intellectual and Developmental Disabilities·Suzanne McDermottLijing Ouyang
Dec 3, 2015·Proceedings of the National Academy of Sciences of the United States of America·Thuy N VienStephen J Moss
Apr 30, 2017·The European Journal of Neuroscience·Yuri BozziSimona Casarosa
May 19, 2017·Epilepsy Research·Rebecca S HammondJames J Doherty
Aug 3, 2017·Journal of Neurodevelopmental Disorders·Andrew LigsayRandi J Hagerman

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Citations

Jun 13, 2020·Frontiers in Molecular Neuroscience·Ioannis KramvisRhiannon M Meredith

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Methods Mentioned

BETA
electron microscopy

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