The novel cyclooxygenase-2 inhibitor GW637185X protects against l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity.
The possible neuroprotective role of a novel and highly selective cyclooxygenase-2 inhibitor GW637185X was studied in a model of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced injury of nigrostriatal dopaminergic (DA) neurons in the mouse. Stereological and microdensitometrical analysis of nigral tyrosine hydroxylase-immunoreactive cell bodies and striatal tyrosine hydroxylase-immunoreactive terminals, respectively, showed that GW637185X exerted a full protection against MPTP-induced degeneration of the nigro-striatal pathway. In contrast to earlier studies, these findings demonstrate that acute inhibition of cyclooxygenase-2 can result in a full neuroprotective effect not only on nigral DA cell bodies, but also on striatal DA terminals in the mouse MPTP model.
Aguirre
Jose A
JA
Department of Human Physiology, School of Medicine, University of Malaga, Malaga, Spain. Jose.Aguirre@uma.es
Leo
Giuseppina
G
Cueto
Raquel
R
Andbjer
Beth
B
Naylor
Alan
A
Medhurst
Andrew D
AD
Agnati
Luigi F
LF
Fuxe
Kjell
K
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D007150:Immunohistochemistry; D020267:MPTP Poisoning / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D018696:Neuroprotective Agents; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine