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MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212

2010; Nature Portfolio; Volume: 13; Issue: 9 Linguagem: Inglês

10.1038/nn.2615

1546-1726

Heh‐In Im, Jonathan A. Hollander, Purva Bali, Paul J. Kenny,

Circular RNAs in diseases

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.