biostudies-literatureZarrouki FConseil Régional d'Île-de-FranceUniversity of Paris-SaclayMinistry of Higher Education and ResearchFrench Muscular Dystrophy AssociationAssociation Monégasque contre les Myopathies (AMM, Monaco)InsermFrench National Centre for Scientific ResearchEuropean Union's Horizon 2020 research and innovation12617https://www.ebi.ac.uk/biostudies/studies/S-EPMC9604073biostudies-literatureUnknown23(20)Duchenne muscular dystrophy (DMD) is a neurodevelopmental disorder primarily caused by the loss of the full-length Dp427 dystrophin in both muscle and brain. The basis of the central comorbidities in DMD is unclear. Brain dystrophin plays a role in the clustering of central gamma-aminobutyric acid A receptors (GABA_ARs), and its loss in the <i>mdx</i> mouse alters the clustering of some synaptic subunits in central inhibitory synapses. However, the diversity of GABAergic alterations in this model is still fragmentary. In this study, the analysis of in vivo PET imaging of a benzodiazepine-binding site radioligand revealed that the global density of central GABA_ARs is unaffected in <i>mdx</i> compared with WT mice. In contrast, semi-quantitative immunoblots and immunofluorescence confocal imaging in tissue sections revealed complex and differential patterns of alterations of the expression levels and/or clustered distribution of a variety of synaptic and extrasynaptic GABA_AR subunits in the hippocampus, cerebellum, cortex, and spinal cord. Hence, dystrophin loss not only affects the stabilization of synaptic GABA_ARs but also influences the subunit composition of GABA_ARs subtypes at both synaptic and extrasynaptic sites. This study provides new molecular outcome measures and new routes to evaluate the impact of treatments aimed at compensating alterations of the nervous system in DMD.International journal of molecular sciencesAbnormal Expression of Synaptic and Extrasynaptic GABA_A Receptor Subunits in the Dystrophin-Deficient <i>mdx</i> Mouse.PMC9604073N/A847826PhD fellowshipGarcia LVaillend CZarrouki FVacca OGoutal SGoyenvalle ATournier NfalseAbnormal Expression of Synaptic and Extrasynaptic GABA_A Receptor Subunits in the Dystrophin-Deficient <i>mdx</i> Mouse.Duchenne muscular dystrophy (DMD) is a neurodevelopmental disorder primarily caused by the loss of the full-length Dp427 dystrophin in both muscle and brain. The basis of the central comorbidities in DMD is unclear. Brain dystrophin plays a role in the clustering of central gamma-aminobutyric acid A receptors (GABA_ARs), and its loss in the <i>mdx</i> mouse alters the clustering of some synaptic subunits in central inhibitory synapses. However, the diversity of GABAergic alterations in this model is still fragmentary. In this study, the analysis of in vivo PET imaging of a benzodiazepine-binding site radioligand revealed that the global density of central GABA_ARs is unaffected in <i>mdx</i> compared with WT mice. In contrast, semi-quantitative immunoblots and immunofluorescence confocal imaging in tissue sections revealed complex and differential patterns of alterations of the expression levels and/or clustered distribution of a variety of synaptic and extrasynaptic GABA_AR subunits in the hippocampus, cerebellum, cortex, and spinal cord. Hence, dystrophin loss not only affects the stabilization of synaptic GABA_ARs but also influences the subunit composition of GABA_ARs subtypes at both synaptic and extrasynaptic sites. This study provides new molecular outcome measures and new routes to evaluate the impact of treatments aimed at compensating alterations of the nervous system in DMD.2022-01-01T00:00:00Z2022 Oct2025-04-04T11:29:22.15Z2025-04-04T11:29:22.15ZS-EPMC96040733629349610.3390/ijms232012617