title: The benzodiazepine Midazolam mitigates the breathing defects of Mecp2-deficient mice.
abstract: Rett syndrome is a severe neurodevelopmental disease caused by mutations of the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2) that induce complex, disabling symptoms, including breathing symptoms. Males of Mecp2-deficient mice (Mecp2(-/y)) normally breathe at birth but develop first altered breathing regulations, thereafter erratic breathing with severe apnoeas, aggravating until respiratory distress and premature death. Mecp2(-/y) mice also develop early GABA deficits. To examine whether GABA deficits contributed to breathing defects of Mecp2(-/y) mice, mice were subjected to acute administration of Midazolam, a benzodiazepine of clinical use known to enhance GABA effects. For the first time, we showed that Midazolam abolished, although transiently, the breathing defects of Mecp2(-/y) mice, confirming a crucial role of GABA deficits in their breathing defects.
authors.affiliation: Unité Mixte de Recherche (UMR) 6231, Centre National de la Recherche Scinetifique, Université de la Méditerranée, Université Paul Cézanne, Faculté Saint Jérôme (Service 362), Marseille, France. nicolas.voituron@univ-paris13.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Voituron
authors.forename: Gérard
authors.initials: G
authors.lastname: Hilaire
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D004195:Disease Models, Animal; D018755:GABA Agonists / Q000494:pharmacology*; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008874:Midazolam / Q000494:pharmacology*; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018755:GABA Agonists; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid; D008874:Midazolam