Publication
Title
The <___tex>$GABA_{A}$ receptor is an FMRP target with therapeutic potential in fragile X syndrome
Author
Abstract
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.
Language
English
Source (journal)
Cell cycle. - Place of publication unknown
Publication
Place of publication unknown : 2015
ISSN
1538-4101
Volume/pages
14:18(2015), p. 2985-2995
ISI
000361527600021
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 07.04.2015
Last edited 18.07.2017
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