title: Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome.
abstract: Fragile X syndrome is a leading heritable cause of mental retardation that results from the loss of FMR1 gene function. A Drosophila model for Fragile X syndrome, based on the loss of dfmr1 activity, exhibits phenotypes that bear similarity to Fragile X-related symptoms. Herein, we demonstrate that treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium can rescue courtship and mushroom body defects observed in these flies. Furthermore, we demonstrate that dfmr1 mutants display cognitive deficits in experience-dependent modification of courtship behavior, and treatment with mGluR antagonists or lithium restores these memory defects. These findings implicate enhanced mGluR signaling as the underlying cause of the cognitive, as well as some of the behavioral and neuronal, phenotypes observed in the Drosophila Fragile X model. They also raise the possibility that compounds having similar effects on metabotropic glutamate receptors may ameliorate cognitive and behavioral defects observed in Fragile X patients.
authors.affiliation: Section of Molecular Cardiology, Department of Medicine, Medical Scientist Training Program, Albert Einstein College of Medicine, Bronx, NY 10461, USA. smcbride@aecom.yu.edu
authors.forename: Sean M J
authors.initials: SM
authors.lastname: McBride
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Choi
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: David
authors.initials: D
authors.lastname: Liebelt
authors.forename: Evan
authors.initials: E
authors.lastname: Braunstein
authors.forename: David
authors.initials: D
authors.lastname: Ferreiro
authors.forename: Amita
authors.initials: A
authors.lastname: Sehgal
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Siwicki
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Dockendorff
authors.forename: Hanh T
authors.initials: HT
authors.lastname: Nguyen
authors.forename: Thomas V
authors.initials: TV
authors.lastname: McDonald
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Jongens
mesh_terms: D000818:Animals; D003380:Courtship / Q000523:psychology; D004195:Disease Models, Animal; D004330:Drosophila; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005600:Fragile X Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology; D008094:Lithium / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D024521:Mushroom Bodies / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D008094:Lithium