GABA and Glutamate Pathways Are Spatially and Developmentally Affected in the Brain of Mecp2-Deficient Mice

Abstract : Proper brain functioning requires a fine-tuning between excitatory and inhibitory neurotransmission, a balance maintained through the regulation and release of glutamate and GABA. Rett syndrome (RTT) is a rare genetic disorder caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene affecting the postnatal brain development. Dysfunctions in the GABAergic and glutamatergic systems have been implicated in the neuropathology of RTT and a disruption of the balance between excitation and inhibition, together with a perturbation of the electrophysiological properties of GABA and glutamate neurons, were reported in the brain of the Mecp2-deficient mouse. However, to date, the extent and the nature of the GABA/glutamate deficit affecting the Mecp2-deficient mouse brain are unclear. In order to better characterize these deficits, we simultaneously analyzed the GABA and glutamate levels in Mecp2-deficient mice at 2 different ages (P35 and P55) and in several brain areas. We used a multilevel approach including the quantification of GABA and glutamate levels, as well as the quantification of the mRNA and protein expression levels of key genes involved in the GABAergic and glutamatergic pathways. Our results show that Mecp2-deficient mice displayed regional-and age-dependent variations in the GABA pathway and, to a lesser extent, in the glutamate pathway. The implication of the GABA pathway in the RTT neuropathology was further confirmed using an in vivo treatment with a GABA reuptake inhibitor that significantly improved the lifespan of Mecp2-deficient mice. Our results confirm that RTT mouse present a deficit in the GABAergic pathway and suggest that GABAergic modulators could be interesting therapeutic agents for this severe neurological disorder.
Type de document :
Article dans une revue
PLoS ONE, Public Library of Science, 2014, 9 (3), pp.e92169. 〈10.1371/journal.pone.0092169〉
Liste complète des métadonnées

Littérature citée [72 références]  Voir  Masquer  Télécharger

https://hal-amu.archives-ouvertes.fr/hal-01668664
Contributeur : Laurent Villard <>
Soumis le : mercredi 28 mars 2018 - 17:25:23
Dernière modification le : lundi 27 août 2018 - 09:44:38
Document(s) archivé(s) le : jeudi 13 septembre 2018 - 11:56:27

Fichier

journal.pone.0092169.PDF
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

Citation

Rita El-Khoury, Nicolas Panayotis, Valérie Matagne, Adeline Ghata, Laurent Villard, et al.. GABA and Glutamate Pathways Are Spatially and Developmentally Affected in the Brain of Mecp2-Deficient Mice. PLoS ONE, Public Library of Science, 2014, 9 (3), pp.e92169. 〈10.1371/journal.pone.0092169〉. 〈hal-01668664〉

Partager

Métriques

Consultations de la notice

124

Téléchargements de fichiers

14