COX-2-deficient mice are less prone to MPTP-neurotoxicity than wild-type mice

Neuroreport. 2003 Oct 27;14(15):1927-9. doi: 10.1097/00001756-200310270-00009.

Abstract

The primary lesion in Parkinson's disease is the death of dopaminergic neurons in the substantia nigra. The role of cyclooxygenase (COX)-2 in the etiology of Parkinson's disease was explored using COX-2 gene knockout mice. Mortality after injection of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP, a chemical known to cause parkinsonism in humans) in heterozygous COX-2-deficient mice was lower than that in wild-type mice. The number of tyrosine hydroxylase immunoreactive neurons in the substantia nigra pars compacta of MPTP-treated wild-type mice declined to a greater extent than in heterozygous mice. Inhibition of COX-2 protein expression decreased the lesion caused by MPTP and protected the dopaminergic neurons in substantia nigra pars compacta. This result suggested that inhibition of COX-2 has potential therapeutic implications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine*
  • Animals
  • Cyclooxygenase 2
  • Dopamine Agents / toxicity*
  • Genotype
  • Isoenzymes / deficiency*
  • Isoenzymes / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / pathology
  • Prostaglandin-Endoperoxide Synthases / deficiency*
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Substantia Nigra / enzymology
  • Substantia Nigra / pathology
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Dopamine Agents
  • Isoenzymes
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Tyrosine 3-Monooxygenase
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases