Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome.
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.
McBride
Sean M J
SM
Section of Molecular Cardiology, Department of Medicine, Medical Scientist Training Program, Albert Einstein College of Medicine, Bronx, NY 10461, USA. smcbride@aecom.yu.edu
Choi
Catherine H
CH
Wang
Yan
Y
Liebelt
David
D
Braunstein
Evan
E
Ferreiro
David
D
Sehgal
Amita
A
Siwicki
Kathleen K
KK
Dockendorff
Thomas C
TC
Nguyen
Hanh T
HT
McDonald
Thomas V
TV
Jongens
Thomas A
TA
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
D018691:Excitatory Amino Acid Antagonists; D008094:Lithium