Cocaine increases phosphorylation of MeCP2 in the rat striatum in vivo

A differential role of NMDA receptors

Li Min Mao, Erica Horton, Minglei Guo, Bing Xue, Dao Zhong Jin, Eugene E. Fibuch, John Q. Wang

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Methyl CpG-binding protein-2 (MeCP2) is a transcriptional regulator that binds to methylated DNA at CpG sites and functions to silence DNA transcription. MeCP2 is subject to the phosphorylation modification at serine 421 (S421), which releases MeCP2 from DNA and thus facilitates gene expression. As a transcriptional repressor densely expressed in limbic reward circuits of adult mammalian brains, MeCP2 is recently emerging as a critical epigenetic factor in experience-dependent neural plasticity and psychostimulant addiction. In this study, we investigated the regulation of MeCP2 phosphorylation in the rat striatum by the psychostimulant cocaine in vivo. We found that acute systemic injection of cocaine increased MeCP2 phosphorylation at S421 in the rat striatum, including both the caudate putamen and the nucleus accumbens, while cocaine did not affect MeCP2 phosphorylation in the medial prefrontal cortex. The cocaine-stimulated MeCP2 phosphorylation in the nucleus accumbens was a rapid and transient event, as it was evident at 20 min and returned to normal levels 3 h after drug injection. The cocaine effect in the caudate putamen was however relatively delayed. Reliable induction of MeCP2 phosphorylation in this region was detected at 60 min. Pretreatment with an N-methyl-d-aspartate (NMDA) glutamate receptor antagonist significantly reduced the cocaine-stimulated MeCP2 phosphorylation in the caudate putamen, although not in the nucleus accumbens. Our data support that MeCP2 is a sensitive target of psychostimulants. Its phosphorylation status is regulated by psychostimulant exposure. NMDA receptors play a region-specific role in linking cocaine to MeCP2 phosphorylation in striatal neurons in vivo.

Original languageEnglish (US)
Pages (from-to)610-617
Number of pages8
JournalNeurochemistry International
Volume59
Issue number5
DOIs
StatePublished - Oct 1 2011

Fingerprint

Methyl-CpG-Binding Protein 2
Cocaine
Phosphorylation
Putamen
Nucleus Accumbens
Serine
rat Mecp2 protein
aspartic acid receptor
DNA
Corpus Striatum
Excitatory Amino Acid Antagonists
Injections
Neuronal Plasticity
Caudate Nucleus
Prefrontal Cortex
Reward
Epigenomics

Keywords

  • Addiction
  • CREB
  • Caudate
  • Dopamine
  • Glutamate
  • Nucleus accumbens
  • Prefrontal cortex
  • Stimulant
  • Transcription

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Cocaine increases phosphorylation of MeCP2 in the rat striatum in vivo : A differential role of NMDA receptors. / Mao, Li Min; Horton, Erica; Guo, Minglei; Xue, Bing; Jin, Dao Zhong; Fibuch, Eugene E.; Wang, John Q.

In: Neurochemistry International, Vol. 59, No. 5, 01.10.2011, p. 610-617.

Research output: Contribution to journalArticle

Mao, Li Min ; Horton, Erica ; Guo, Minglei ; Xue, Bing ; Jin, Dao Zhong ; Fibuch, Eugene E. ; Wang, John Q. / Cocaine increases phosphorylation of MeCP2 in the rat striatum in vivo : A differential role of NMDA receptors. In: Neurochemistry International. 2011 ; Vol. 59, No. 5. pp. 610-617.
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