Title
Expression of the GABAergic system in animal models for fragile X syndrome and fragile X associated tremor/ataxia syndrome (FXTAS) Expression of the GABAergic system in animal models for fragile X syndrome and fragile X associated tremor/ataxia syndrome (FXTAS)
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Amsterdam ,
Subject
Human medicine
Source (journal)
Brain research. - Amsterdam
Volume/pages
1253(2009) , p. 176-183
ISSN
0921-8246
0006-8993
ISI
000263738600019
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
After our initial discovery of reduced expression of several subunits of the GABAA receptor in two different animal models for fragile X syndrome, a frequent form of inherited mental retardation, we analyzed further components of the GABAergic pathway. Interestingly, we found a down regulation of many additional elements of the GABA signalling system, strengthening our hypothesis of involvement of the GABAergic pathway in the pathophysiology of fragile X syndrome. This is of special interest with regard to new therapeutic opportunities for treatment of this disorder. Remarkably, under expression was predominantly observed in cortex, although some elements of the GABAergic system that are expressed presynaptically or in the glial cells were also down regulated in the cerebellum. Additionally, we assessed the GABAergic system in expanded CGG-repeat mice, a model for fragile X associated tremor/ataxia syndrome (FXTAS). This late onset neurodegenerative disorder occurs in carriers of the fragile X premutation (55200 CGG repeats) and is completely distinct (from both clinical and molecular pathogenic perspectives) from the neurodevelopmental disorder fragile X syndrome. Here we found upregulation of many components of the GABAergic system in cerebellum, but not in cortex. This finding is consistent with the cerebellar phenotype of FXTAS patients and has implications for the mechanism causative of differential gene expression.
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