HDAC inhibitor ameliorates behavioral deficits in Mecp2308/y mouse model of Rett syndrome.
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 Mecp2308/y mice. These findings are a first step toward the validation of a novel treatment for RTT.
['Lebrun|Nicolas|N|', 'Delépine|Chloé|C|', 'Selloum|Mohamed|M|', 'Meziane|Hamid|H|', 'Nectoux|Juliette|J|', 'Herault|Yann|Y|', 'Bienvenu|Thierry|T|']
Rett syndrome MeCP2 Microtubules Astrocytes Tubastatin A HDAC6