Ethyl pyruvate rescues nigrostriatal dopaminergic neurons by regulating glial activation in a mouse model of Parkinson's disease

J Immunol. 2011 Jul 15;187(2):960-9. doi: 10.4049/jimmunol.1100009. Epub 2011 Jun 17.


This study examined whether ethyl pyruvate (EP) promotes the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. MPTP induced degeneration of nigrostriatal DA neurons and glial activation as visualized by tyrosine hydroxylase, macrophage Ag complex-1, and/or glial fibrillary acidic protein immunoreactivity. Western blotting and immunohistochemistry showed activation of microglial NADPH oxidase and astroglial myeloperoxidase (MPO) and subsequent reactive oxygen species/reactive nitrogen species production and oxidative DNA damage in the MPTP-treated substantia nigra. Treatment with EP prevented degeneration of nigrostriatal DA neurons, increased striatal dopamine levels, and improved motor function. This neuroprotection afforded by EP was associated with the suppression of astroglial MPO expression, NADPH oxidase-, and/or inducible NO synthase-derived reactive oxygen species/reactive nitrogen species production by activated microglia. Interestingly, EP was found to protect DA neurons from 1-methyl-4-phenyl-pyridinium neurotoxicity in cocultures of mesencephalic neurons and microglia but not in neuron-enriched mesencephalic cultures devoid of microglia. The present findings show that EP may inhibit glial-mediated oxidative stress, suggesting that EP may have therapeutic value in the treatment of aspects of Parkinson's disease related to glia-derived oxidative damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / administration & dosage
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / antagonists & inhibitors
  • Animals
  • Cells, Cultured
  • Coculture Techniques
  • Corpus Striatum / drug effects
  • Corpus Striatum / immunology
  • Corpus Striatum / pathology
  • Disease Models, Animal
  • Dopamine / adverse effects
  • Dopamine / physiology*
  • Dopamine Antagonists / administration & dosage
  • Dopamine Antagonists / therapeutic use
  • Inflammation Mediators / administration & dosage
  • Inflammation Mediators / antagonists & inhibitors
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuroglia / drug effects
  • Neuroglia / immunology*
  • Neuroglia / pathology
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Oxidative Stress / immunology
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / immunology*
  • Parkinson Disease / pathology
  • Pyruvates / administration & dosage
  • Pyruvates / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Substantia Nigra / drug effects
  • Substantia Nigra / immunology*
  • Substantia Nigra / pathology


  • Dopamine Antagonists
  • Inflammation Mediators
  • Pyruvates
  • ethyl pyruvate
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Dopamine