Rescue of Methyl-CpG Binding Protein 2 Dysfunction-induced Defects in Newborn Neurons by Pentobarbital.

Journal Article (Journal Article)

Rett syndrome is a neurodevelopmental disorder that usually arises from mutations or deletions in methyl-CpG binding protein 2 (MeCP2), a transcriptional regulator that affects neuronal development and maturation without causing cell loss. Here, we show that silencing of MeCP2 decreased neurite arborization and synaptogenesis in cultured hippocampal neurons from rat fetal brains. These structural defects were associated with alterations in synaptic transmission and neural network activity. Similar retardation of dendritic growth was also observed in MeCP2-deficient newborn granule cells in the dentate gyrus of adult mouse brains in vivo, demonstrating direct and cell-autonomous effects on individual neurons. These defects, caused by MeCP2 deficiency, were reversed by treatment with the US Food and Drug Administration-approved drug, pentobarbital, in vitro and in vivo, possibly caused by modulation of γ-aminobutyric acid signaling. The results indicate that drugs modulating γ-aminobutyric acid signaling are potential therapeutics for Rett syndrome.

Full Text

Duke Authors

Cited Authors

  • Ma, D; Yoon, S-I; Yang, C-H; Marcy, G; Zhao, N; Leong, W-Y; Ganapathy, V; Han, J; Van Dongen, AMJ; Hsu, K-S; Ming, G-L; Augustine, GJ; Goh, ELK

Published Date

  • April 2015

Published In

Volume / Issue

  • 12 / 2

Start / End Page

  • 477 - 490

PubMed ID

  • 25753729

Pubmed Central ID

  • PMC4404443

Electronic International Standard Serial Number (EISSN)

  • 1878-7479

Digital Object Identifier (DOI)

  • 10.1007/s13311-015-0343-0


  • eng

Conference Location

  • United States