title: Meloxicam reduces lipopolysaccharide-induced degeneration of dopaminergic neurons in the rat substantia nigra pars compacta.
abstract: 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.
authors.affiliation: Florey Neuroscience Institutes, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sui
authors.forename: Davor
authors.initials: D
authors.lastname: Stanić
authors.forename: Doris
authors.initials: D
authors.lastname: Tomas
authors.forename: Bevyn
authors.initials: B
authors.lastname: Jarrott
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Horne
mesh_terms: 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
chemical_list: D039481:CD11b Antigen; D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D013843:Thiazines; D013844:Thiazoles; D014446:Tyrosine 3-Monooxygenase; D000077239:Meloxicam; D004298:Dopamine