Edaravone guards dopamine neurons in a rotenone model for Parkinson's disease

PLoS One. 2011;6(6):e20677. doi: 10.1371/journal.pone.0020677. Epub 2011 Jun 3.

Abstract

3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone), an effective free radical scavenger, provides neuroprotection in stroke models and patients. In this study, we investigated its neuroprotective effects in a chronic rotenone rat model for Parkinson's disease. Here we showed that a five-week treatment with edaravone abolished rotenone's activity to induce catalepsy, damage mitochondria and degenerate dopamine neurons in the midbrain of rotenone-treated rats. This abolishment was attributable at least partly to edaravone's inhibition of rotenone-induced reactive oxygen species production or apoptotic promoter Bax expression and its up-regulation of the vesicular monoamine transporter 2 (VMAT2) expression. Collectively, edaravone may provide novel clinical therapeutics for PD.

Publication types

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

MeSH terms

  • Animals
  • Antipyrine / analogs & derivatives*
  • Antipyrine / pharmacology
  • Antipyrine / therapeutic use
  • Behavior, Animal / drug effects
  • Dopamine / metabolism*
  • Edaravone
  • Free Radical Scavengers / pharmacology
  • Free Radical Scavengers / therapeutic use*
  • Freezing Reaction, Cataleptic / drug effects
  • Humans
  • Male
  • Neurons / drug effects*
  • Neurons / physiology
  • Neurons / ultrastructure
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Neuropsychological Tests
  • Parkinsonian Disorders / chemically induced*
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / pathology
  • Parkinsonian Disorders / physiopathology
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Rotenone / pharmacology*
  • Uncoupling Agents / pharmacology
  • Vesicular Monoamine Transport Proteins / genetics
  • Vesicular Monoamine Transport Proteins / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Free Radical Scavengers
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Slc18a2 protein, rat
  • Uncoupling Agents
  • Vesicular Monoamine Transport Proteins
  • bcl-2-Associated X Protein
  • Rotenone
  • Edaravone
  • Antipyrine
  • Dopamine