title: MeCP2 in the rostral striatum maintains local dopamine content critical for psychomotor control.
abstract: Methyl-CpG binding protein 2 (MeCP2) is a chromatin regulator highly expressed in mature neurons. Mutations of MECP2 gene cause >90% cases of Rett syndrome, a neurodevelopmental disorder featured by striking psychomotor dysfunction. In Mecp2-null mice, the motor deficits are associated with reduction of dopamine content in the striatum, the input nucleus of basal ganglia mostly composed of GABAergic neurons. Here we investigated the causal role of MeCP2 in modulation of striatal dopamine content and psychomotor function. We found that mice with selective removal of MeCP2 in forebrain GABAergic neurons, predominantly in the striatum, phenocopied Mecp2-null mice in dopamine deregulation and motor dysfunction. Selective expression of MeCP2 in the striatum preserved dopamine content and psychomotor function in both males and females. Notably, the dopamine deregulation was primarily confined to the rostral striatum, and focal deletion or reactivation of MeCP2 expression in the rostral striatum through adeno-associated virus effectively disrupted or restored dopamine content and locomotor activity, respectively. Together, these findings demonstrate that striatal MeCP2 maintains local dopamine content in a non-cell autonomous manner in the rostral striatum and that is critical for psychomotor control.
authors: Institute of Neuroscience and.
authors: San-Hua
authors: SH
authors: Su
authors: Institute of Neuroscience and.
authors: Fang-Chi
authors: FC
authors: Kao
authors: Institute of Neuroscience and.
authors: Yi-Bo
authors: YB
authors: Huang
authors: Institute of Neuroscience and Research Center for Mind, Brain, and Learning, National Cheng-Chi University, Taipei 11605, Taiwan wlliao@nccu.edu.tw.
authors: Wenlin
authors: W
authors: Liao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009154:Mutation / Q000235:genetics; D011597:Psychomotor Performance / Q000502:physiology*; D014161:Transduction, Genetic
chemical_list: C501120:Dlx5 protein, mouse; D018398:Homeodomain Proteins; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D004298:Dopamine
keywords: Rett syndrome; dopamine; methyl-CpG binding protein 2; motor control; striatum