COX-2-deficient mice are less prone to MPTP-neurotoxicity than wild-type mice.
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.
Feng
Zhehui
Z
University Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong. zfeng@mdanderson.org
Li
Dongdong
D
Fung
Peter C W
PC
Pei
Zhong
Z
Ramsden
David B
DB
Ho
Shu-Leong
SL
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D051546:Cyclooxygenase 2; D015259:Dopamine Agents / Q000633:toxicity*; D005838:Genotype; D007527:Isoenzymes / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013378:Substantia Nigra / Q000201:enzymology / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015259:Dopamine Agents; D007527:Isoenzymes; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases