Fiche publication
Date publication
septembre 2021
Journal
Brain research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr HERAULT Yann
Tous les auteurs :
Lebrun N, Delépine C, Selloum M, Meziane H, Nectoux J, Herault Y, Bienvenu T
Lien Pubmed
Résumé
Rett syndrome (RTT) is a rare X-linked neurodevelopmental disorder. More than 95% of classic RETT syndrome cases result from pathogenic variants in the methyl-CpG binding protein 2 (MECP2) gene. Nevertheless, it has been established that a spectrum of neuropsychiatric phenotypes is associated with MECP2 variants in both females and males. We previously reported that microtubule growth velocity and vesicle transport directionality are altered in Mecp2-deficient astrocytes from newborn Mecp2-deficient mice compared to that of their wild-type littermates suggesting deficit in microtubule dynamics. In this study, we report that administration of tubastatin A, a selective HDAC6 inhibitor, restored microtubule dynamics in Mecp2-deficient astrocytes. We furthermore report that daily doses of tubastatin A reversed early impaired exploratory behavior in male Mecp2 mice. These findings are a first step toward the validation of a novel treatment for RTT.
Mots clés
Astrocytes, HDAC6, Microtubules, Rett syndrome . MeCP2, Tubastatin A
Référence
Brain Res. 2021 Sep 25;:147670
