Additive neuroprotective effects of creatine and a cyclooxygenase 2 inhibitor against dopamine depletion in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease

J Mol Neurosci. 2003;21(3):191-8. doi: 10.1385/jmn:21:3:191.

Abstract

There is evidence that both inflammatory mechanisms and mitochondrial dysfunction contribute to Parkinson's disease (PD) pathogenesis. We investigated whether the cyclooxygenase 2 (COX-2) inhibitor rofecoxib either alone or in combination with creatine could exert neuroprotective effects in the 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine model of PD in mice. Both rofecoxib and creatine administered alone protected against striatal dopamine depletions and loss of substantia nigra tyrosine hydroxylase immunoreactive neurons. Administration of rofecoxib with creatine produced significant additive neuroprotective effects against dopamine depletions. These results suggest that a combination of a COX-2 inhibitor with creatine might be a useful neuroprotective strategy for PD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Creatine / pharmacology*
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • Disease Models, Animal
  • Dopamine / deficiency*
  • Drug Synergism
  • Drug Therapy, Combination
  • Free Radicals / antagonists & inhibitors
  • Inflammation / drug therapy
  • Inflammation / enzymology
  • Inflammation / physiopathology
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Lactones / pharmacology
  • Male
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / enzymology
  • Neuroprotective Agents / pharmacology*
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / enzymology
  • Parkinsonian Disorders / physiopathology
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Substantia Nigra / drug effects
  • Substantia Nigra / enzymology
  • Sulfones
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Free Radicals
  • Isoenzymes
  • Lactones
  • Neuroprotective Agents
  • Sulfones
  • rofecoxib
  • Tyrosine 3-Monooxygenase
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Creatine
  • Dopamine