The impact of MeCP2 loss-or gain-of-function on synaptic plasticity

Elisa S. Na, Erika D. Nelson, Ege T Kavalali, Lisa M Monteggia

Research output: Contribution to journalReview articlepeer-review

127 Scopus citations

Abstract

Methyl-CpG-binding protein 2 (MeCP2) is a transcriptional regulator of gene expression that is an important epigenetic factor in the maintenance and development of the central nervous system. The neurodevelopmental disorders Rett syndrome and MECP2 duplication syndrome arise from loss-of-function and gain-of-function alterations in MeCP2 expression, respectively. Several animal models have been developed to recapitulate the symptoms of Rett syndrome and MECP2 duplication syndrome. Cell morphology, neurotransmission, and cellular processes that support learning and memory are compromised as a result of MeCP2 loss- or gain-of-function. Interestingly, loss-of-MeCP2 function and MeCP2 overexpression trigger diametrically opposite changes in synaptic transmission. These findings indicate that the precise regulation of MeCP2 expression is a key requirement for the maintenance of synaptic and neuronal homeostasis and underscore its importance in central nervous system function. This review highlights the functional role of MeCP2 in the brain as a regulator of synaptic and neuronal plasticity as well as its etiological role in the development of Rett syndrome and MECP2 duplication syndrome.

Original languageEnglish (US)
Pages (from-to)212-219
Number of pages8
JournalNeuropsychopharmacology
Volume38
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • MeCP2 duplication syndrome
  • Rett syndrome
  • behavior
  • long-term potentiation
  • synaptic transmission

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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