Rescue of Methyl-CpG Binding Protein 2 Dysfunction-induced Defects in Newborn Neurons by Pentobarbital
Year: 2015
Type: article
Abstract: 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.
Source: Neurotherapeutics
Institutions: National University of Singapore, Duke-NUS Medical School, Nanyang Technological University, National Cheng Kung University, Xi'an Jiaotong University, Johns Hopkins University, Johns Hopkins Medicine, Agency for Science, Technology and Research, Korea Institute of Science and Technology, Institute of Molecular and Cell Biology, KK Women's and Children's Hospital
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,900
Funders: National Research Foundation, National Research Foundation Singapore, National Research Foundation of Korea, Ministry of Education, Science and Technology, National Institutes of Health, Medical Research Council, National Medical Research Council, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development
OpenAlex ID: W2010915890