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The <___tex>$GABA_{A}$ receptor is an FMRP target with therapeutic potential in fragile X syndrome

Tijdschriftbijdrage - Tijdschriftartikel

Previous research indicates that the GABAAergic system is involved in the pathophysiology of the fragile X syndrome, a frequent form of inherited intellectual disability and associated with autism spectrum disorder. However, the molecular mechanism underlying GABAAergic deficits has remained largely unknown. Here, we demonstrate reduced mRNA expression of GABAA receptor subunits in the cortex and cerebellum of young Fmr1 knockout mice. In addition, we show that the previously reported underexpression of specific subunits of the GABAA receptor can be corrected in YAC transgenic rescue mice, containing the full-length human FMR1 gene in an Fmr1 knockout background. Moreover, we demonstrate that FMRP directly binds several GABAA receptor mRNAs. Finally, positive allosteric modulation of GABAA receptors with the neurosteroid ganaxolone can modulate specific behaviours in Fmr1 knockout mice, emphasizing the therapeutic potential of the receptor.
Tijdschrift: Cell cycle
ISSN: 1538-4101
Volume: 14
Pagina's: 2985 - 2995
Jaar van publicatie:2015
Trefwoorden:A1 Journal article
BOF-keylabel:ja
BOF-publication weight:1
CSS-citation score:2
Auteurs:International
Authors from:Higher Education
Toegankelijkheid:Open