Ma, Dongliang Yoon, Su-In Yang, Chih-Hao Marcy, Guillaume Zhao, Na Leong, Wan-Ying Ganapathy, Vinu Han, Ju Van Dongen, Antonius M. J. Hsu, Kuei-Sen Ming, Guo-Li Augustine, George J. Goh, Eyleen L. K. 2024-01-20T07:30:28Z 2024-01-20T07:30:28Z 2022-01-25 2015-04 1933-7213 https://pubs.kist.re.kr/handle/201004/125568 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 gamma-aminobutyric acid signaling. The results indicate that drugs modulating gamma-aminobutyric acid signaling are potential therapeutics for Rett syndrome. English SPRINGER Rescue of Methyl-CpG Binding Protein 2 Dysfunction-induced Defects in Newborn Neurons by Pentobarbital Article 10.1007/s13311-015-0343-0 1 NEUROTHERAPEUTICS, v.12, no.2, pp.477 - 490 NEUROTHERAPEUTICS 12 2 477 490 N scie scopus 000353223000019 2-s2.0-84939968942 Clinical Neurology Neurosciences Pharmacology & Pharmacy Neurosciences & Neurology Pharmacology & Pharmacy Article MECP2 MUTANT MICE RETT-SYNDROME MOUSE MODEL TRANSCRIPTIONAL REPRESSOR SYNAPTIC PLASTICITY HIPPOCAMPAL-NEURONS NONSENSE MUTATIONS CA2+ OSCILLATIONS BRAIN GABA(A) Rett syndrome newborn neurons dendrites GABA pentobarbital