title: Pharmacological reversal of synaptic plasticity deficits in the mouse model of fragile X syndrome by group II mGluR antagonist or lithium treatment.
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.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Choi
authors.forename: Brian P
authors.initials: BP
authors.lastname: Schoenfeld
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Bell
authors.forename: Paul
authors.initials: P
authors.lastname: Hinchey
authors.forename: Maria
authors.initials: M
authors.lastname: Kollaros
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gertner
authors.forename: Newton H
authors.initials: NH
authors.lastname: Woo
authors.forename: Michael R
authors.initials: MR
authors.lastname: Tranfaglia
authors.forename: Mark F
authors.initials: MF
authors.lastname: Bear
authors.forename: R Suzanne
authors.initials: RS
authors.lastname: Zukin
authors.forename: Thomas V
authors.initials: TV
authors.lastname: McDonald
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Jongens
authors.forename: Sean M J
authors.initials: SM
authors.lastname: McBride
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D005600:Fragile X Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018020:Lithium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000235:genetics
chemical_list: D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D018020:Lithium Compounds; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2