title: 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.
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.
authors.affiliation: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, NY 10021, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Klivenyi
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Gardian
authors.forename: Noel Y
authors.initials: NY
authors.lastname: Calingasan
authors.forename: Lichuan
authors.initials: L
authors.lastname: Yang
authors.forename: M Flint
authors.initials: MF
authors.lastname: Beal
mesh_terms: D000818:Animals; D003401:Creatine / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000172:deficiency*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005609:Free Radicals / Q000037:antagonists & inhibitors; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology; D013450:Sulfones; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005609:Free Radicals; D007527:Isoenzymes; D007783:Lactones; D018696:Neuroprotective Agents; D013450:Sulfones; C116926:rofecoxib; D014446:Tyrosine 3-Monooxygenase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D003401:Creatine; D004298:Dopamine