GABAA a receptor antagonism ameliorates behavioral and synaptic impairments associated with MeCP2 overexpression

Elisa S. Na, Michael J. Morris, Erika D. Nelson, Lisa M Monteggia

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Methyl-CpG-binding protein 2 (MeCP2) is a ubiquitously expressed transcriptional regulator with functional importance in the central nervous system. Loss-of-function mutations in MECP2 results in the neurodevelopmental disorder, Rett syndrome, whereas increased expression levels are associated with the neurological disorder, MECP2 duplication syndrome. Previous characterization of a mouse line overexpressing Mecp2 demonstrated that this model recapitulated key behavioral features of MECP2 duplication syndrome with specific deficits in synaptic plasticity and neurotransmission. Alterations in excitation/inhibition balance have been suggested to underlie neurodevelopmental disorders with recent data suggesting that picrotoxin (PTX), a GABA A receptor antagonist, rescues certain behavioral and synaptic phenotypes in a mouse model of Down syndrome. We therefore examined whether a similar treatment regimen would impact the behavioral and synaptic phenotypes in a mouse model of MECP2 duplication syndrome. We report that chronic treatment with low doses of PTX ameliorates specific behavioral phenotypes, including motor coordination, episodic memory impairments, and synaptic plasticity deficits. These findings suggest that GABA A receptor antagonists may offer a possible therapeutic target for the treatment of MECP2 duplication syndrome.

Original languageEnglish (US)
Pages (from-to)1946-1954
Number of pages9
JournalNeuropsychopharmacology
Volume39
Issue number8
DOIs
StatePublished - 2014

Fingerprint

Methyl-CpG-Binding Protein 2
GABA-A Receptors
GABA-A Receptor Antagonists
Picrotoxin
Neuronal Plasticity
Phenotype
Rett Syndrome
Episodic Memory
Down Syndrome
Nervous System Diseases
Synaptic Transmission
Central Nervous System
Mutation
Lubs X-linked mental retardation syndrome

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Medicine(all)

Cite this

GABAA a receptor antagonism ameliorates behavioral and synaptic impairments associated with MeCP2 overexpression. / Na, Elisa S.; Morris, Michael J.; Nelson, Erika D.; Monteggia, Lisa M.

In: Neuropsychopharmacology, Vol. 39, No. 8, 2014, p. 1946-1954.

Research output: Contribution to journalArticle

Na, Elisa S. ; Morris, Michael J. ; Nelson, Erika D. ; Monteggia, Lisa M. / GABAA a receptor antagonism ameliorates behavioral and synaptic impairments associated with MeCP2 overexpression. In: Neuropsychopharmacology. 2014 ; Vol. 39, No. 8. pp. 1946-1954.
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