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MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212
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MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212
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Journal Article
MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212
2010
Overview
The authors implicate the transcriptional repressor methyl CpG–binding protein MeCP2 in cocaine addiction. They report that MeCP2 regulates cocaine intake through microRNA-212 to control cocaine's effects on strital BDNF levels.
The X-linked transcriptional repressor methyl CpG binding protein 2 (MeCP2), known for its role in the neurodevelopmental disorder Rett syndrome, is emerging as an important regulator of neuroplasticity in postmitotic neurons. Cocaine addiction is commonly viewed as a disorder of neuroplasticity, but the potential involvement of MeCP2 has not been explored. Here we identify a key role for MeCP2 in the dorsal striatum in the escalating cocaine intake seen in rats with extended access to the drug, a process that mimics the increasingly uncontrolled cocaine use seen in addicted humans. MeCP2 regulates cocaine intake through homeostatic interactions with microRNA-212 (miR-212) to control the effects of cocaine on striatal brain-derived neurotrophic factor (BDNF) levels. These data suggest that homeostatic interactions between MeCP2 and miR-212 in dorsal striatum may be important in regulating vulnerability to cocaine addiction.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animal Genetics and Genomics
/ Animals
/ Behavior
/ Biomedical and Life Sciences
/ Brain
/ Brain-derived neurotrophic factor
/ Brain-Derived Neurotrophic Factor - genetics
/ Brain-Derived Neurotrophic Factor - metabolism
/ Cocaine
/ Cocaine-Related Disorders - genetics
/ Cocaine-Related Disorders - metabolism
/ Compulsive Behavior - genetics
/ Compulsive Behavior - metabolism
/ Corpus Striatum - drug effects
/ Corpus Striatum - metabolism
/ Dopamine Uptake Inhibitors - pharmacology
/ Male
/ Methyl-CpG-Binding Protein 2 - genetics
/ Methyl-CpG-Binding Protein 2 - metabolism
/ MicroRNA
/ Proteins
/ Rats
