Meloxicam reduces lipopolysaccharide-induced degeneration of dopaminergic neurons in the rat substantia nigra pars compacta.
Inflammation is believed to play an important role in the etiology and pathogenesis of Parkinson's disease (PD). However, experimental and epidemiological evidences from various non-steroidal anti-inflammatory drugs, including cyclooxygenase-2 (COX-2) inhibitors, seem contradictive. Using the intranigral lipopolysaccharide (LPS) rat model, we show that meloxicam, a preferential COX-2 inhibitor, diminishes the activation of OX-42-immunoreactive (ir) microglia and reduces the loss of tyrosine hydroxylase (TH)-ir dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) that is normally induced by exposure to LPS. Double-labelling immunohistochemistry identified that activated microglia rather than intact resting microglia are the main intracellular venues for COX-2 expression. These findings suggest that inhibition of COX-2 activity in activated microglial cells may be potentially neuroprotective for DA neurons in the SNpc.
Sui
Yi
Y
Florey Neuroscience Institutes, The University of Melbourne, Parkville, Victoria 3010, Australia.
Stanić
Davor
D
Tomas
Doris
D
Jarrott
Bevyn
B
Horne
Malcolm K
MK
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D000077239:Meloxicam; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology*; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000473:pathology*; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D039481:CD11b Antigen; D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D013843:Thiazines; D013844:Thiazoles; D014446:Tyrosine 3-Monooxygenase; D000077239:Meloxicam; D004298:Dopamine