Elevated levels of the vesicular monoamine transporter and a novel repetitive behavior in the Drosophila model of fragile X syndrome

PLoS One. 2011;6(11):e27100. doi: 10.1371/journal.pone.0027100. Epub 2011 Nov 2.

Abstract

Fragile X Syndrome (FXS) is characterized by mental impairment and autism in humans, and it often features hyperactivity and repetitive behaviors. The mechanisms for the disease, however, remain poorly understood. Here we report that the dfmr1 mutant in the Drosophila model of FXS grooms excessively, which may be regulated differentially by two signaling pathways. Blocking metabotropic glutamate receptor signaling enhances grooming in dfmr1 mutant flies, whereas blocking the vesicular monoamine transporter (VMAT) suppresses excessive grooming. dfmr1 mutant flies also exhibit elevated levels of VMAT mRNA and protein. These results suggest that enhanced monoamine signaling correlates with repetitive behaviors and hyperactivity associated with FXS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Disease Models, Animal
  • Drosophila Proteins
  • Drosophila melanogaster / metabolism*
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / etiology
  • Fragile X Syndrome / physiopathology*
  • Grooming
  • Obsessive Behavior / etiology*
  • RNA, Messenger / analysis
  • Signal Transduction
  • Vesicular Monoamine Transport Proteins / analysis
  • Vesicular Monoamine Transport Proteins / metabolism*

Substances

  • Drosophila Proteins
  • FMR1 protein, Drosophila
  • RNA, Messenger
  • Vesicular Monoamine Transport Proteins
  • Fragile X Mental Retardation Protein