Pharmacological reversal of synaptic plasticity deficits in the mouse model of Fragile X syndrome by group II mGluR antagonist or lithium treatment

Catherine H. Choi, Brian P. Schoenfeld, Aaron J. Bell, Paul Hinchey, Maria Kollaros, Michael J. Gertner, Newton H. Woo, Michael R. Tranfaglia, Mark F. Bear, R. Suzanne Zukin, Thomas V. McDonald, Thomas A. Jongens, Sean M.J. McBride

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Fragile X syndrome is the leading single gene cause of intellectual disabilities. Treatment of a Drosophila model of Fragile X syndrome with metabotropic glutamate receptor (mGluR) antagonists or lithium rescues social and cognitive impairments. A hallmark feature of the Fragile X mouse model is enhanced mGluR-dependent long-term depression (LTD) at Schaffer collateral to CA1 pyramidal synapses of the hippocampus. Here we examine the effects of chronic treatment of Fragile X mice in vivo with lithium or a group II mGluR antagonist on mGluR-LTD at CA1 synapses. We find that long-term lithium treatment initiated during development (5-6 weeks of age) and continued throughout the lifetime of the Fragile X mice until 9-11 months of age restores normal mGluR-LTD. Additionally, chronic short-term treatment beginning in adult Fragile X mice (8 weeks of age) with either lithium or an mGluR antagonist is also able to restore normal mGluR-LTD. Translating the findings of successful pharmacologic intervention from the Drosophila model into the mouse model of Fragile X syndrome is an important advance, in that this identifies and validates these targets as potential therapeutic interventions for the treatment of individuals afflicted with Fragile X syndrome.

Original languageEnglish (US)
Pages (from-to)106-119
Number of pages14
JournalBrain Research
Volume1380
DOIs
Publication statusPublished - Mar 22 2011

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Keywords

  • Fragile X syndrome
  • LY341495
  • Lithium
  • Long-term depression
  • Metabotropic glutamate receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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