Rescue of Methyl-CpG Binding Protein 2 Dysfunction-induced Defects in Newborn Neurons by Pentobarbital.
Published
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
- 25753729
Electronic International Standard Serial Number (EISSN)
- 1878-7479
Digital Object Identifier (DOI)
- 10.1007/s13311-015-0343-0
Language
- eng
Conference Location
- United States