MeCP2 in the Rostral Striatum Maintains Local Dopamine Content Critical for Psychomotor Control
| Autor: | San-Hua Su, Yi-Bo Huang, Fang-Chi Kao, Wenlin Liao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
congenital hereditary and neonatal diseases and abnormalities Methyl-CpG-Binding Protein 2 Dopamine Mice Transgenic Striatum Biology Motor Activity MECP2 Mice Transduction Genetic Basal ganglia mental disorders medicine Animals Maze Learning Chromatography High Pressure Liquid Cerebral Cortex Homeodomain Proteins Psychomotor function Analysis of Variance General Neuroscience Articles Corpus Striatum nervous system diseases Psychomotor control nervous system Forebrain Mutation Exploratory Behavior GABAergic Neuroscience Psychomotor Performance medicine.drug |
| Popis: | Methyl-CpG binding protein 2 (MeCP2) is a chromatin regulator highly expressed in mature neurons. Mutations ofMECP2gene cause >90% cases of Rett syndrome, a neurodevelopmental disorder featured by striking psychomotor dysfunction. InMecp2-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, phenocopiedMecp2-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. |
| Databáze: | OpenAIRE |
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