Loss of brain dystrophin alters GABA receptors.

ABNORMAL EXPRESSION OF SYNAPTIC AND EXTRASYNAPTIC GABAA RECEPTOR SUBUNITS IN THE DYSTROPHIN-DEFICIENT MDX MOUSE Duchenne muscular dystrophy (DMD) is a neurodevelopmental syndrome caused by the loss of dystrophin (Dp427) in muscle and brain. The origin of the cognitive and behavioural disorders in DMD is unclear, but is thought to depend in part on the role played by dystrophin in the clustering of central GABA receptors (GABAAR). However, our knowledge of GABAergic alterations in this disease is still fragmentary.

In an article published in the International Journal of Molecular Sciences, Cyrille Vaillend’s team (Institut des Neurosciences Paris-Saclay – NeuroPSI, CNRS/UPSaclay, Orsay), in collaboration with Nicolas Tournier’s teams (BioMaps unit, INSERM/CNRS/CEA-Joliot/UPSaclay, Orsay) and Aurélie Goyenvalle (END-ICAP, UMR-S 1179 INSERM/UVSQ/UPSaclat, Montigny-le-Bretonneux), carried out a detailed analysis of these alterations in the Dp427-deficient mdx mouse. In vivo PET imaging analysis of a benzodiazepine-binding radioligand revealed that the overall density of central GABAARs is not affected in mdx mice. In contrast, semi-quantitative immunoblots and confocal imaging of tissue sections revealed a complex pattern of alterations in the expression levels and/or distribution of various subunits of synaptic and extrasynaptic GABAARs in the hippocampus, cerebellum, cortex and spinal cord.
Loss of dystrophin therefore not only affects the stabilisation of synaptic GABAARs, but also influences the composition of GABAAR subunits at synaptic and extrasynaptic levels. This study provides new molecular biomarkers and new avenues to evaluate the impact of treatments to compensate for brain alterations in DMD.

Abnormal Expression of Synaptic and Extrasynaptic GABAA Receptor Subunits in the Dystrophin-Deficient mdx Mouse. Faouzi Zarrouki, Sébastien Goutal, Ophélie Vacca, Luis Garcia, Nicolas Tournier, Aurélie Goyenvalle and Cyrille Vaillend.

Article published in International Journal of Molecular SciencesAccess to the manuscript