Different parkinsonism models produce a time-dependent induction of COX-2 in the substantia nigra of rats.
The present study investigated the effects on general activity, COX-2 and TH protein expression of intranigral neurotoxins LPS, MPTP or 6-OHDA infusion in rats. Results indicate that LPS produced an increase in locomotion frequency (3 and 7 days after surgery) and a strong up-regulation of COX-2 protein 16 and 24 h after surgery, as observed in the substantia nigra (SN). The MPTP model generated impairment in locomotion frequency 24 h after surgery. Besides, MPTP caused a marked up-regulation in COX-2 protein observed in the SN 16 h after surgery. Moreover, the 6-OHDA model produced severe motor impairment indicated by the decrease in locomotion (24 h) and rearing (24 h, 3 and 7 days) frequencies and also an increase in latency (24 h, 3 and 7 days) and immobility (24 h and 3 days) times. We also demonstrated an up-regulation of COX-2, which occurred in the SN 4-24 h after surgery. TH protein did not appear to be reduced in the striatum in the groups lesioned with the neurotoxins. In contrast, the TH content of SN was significantly reduced in the groups lesioned with the very same neurotoxins. For all the models analyzed, we observed no statistical differences in the expression of COX-2 in the striatum along the time-points. The results of the present study suggest that COX-2 induction patterns differ in function of the neurotoxin tested. Such time-dependent induction has been found to be relatively constant, a fact of great significance considering the importance of the neuroinflammatory process in Parkinson's disease.
de Meira Santos Lima
Marcelo
M
Departamento de Farmacologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Caixa Postal 19031, 81531-980 Curitiba, PR, Brazil.
Braga Reksidler
Angela
A
Marques Zanata
Sílvio
S
Bueno Machado
Hidevaldo
H
Tufik
Sergio
S
Vital
Maria A B F
MA
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D046353:Immobility Response, Tonic / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D008124:Locomotion / Q000187:drug effects; D020267:MPTP Poisoning; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013378:Substantia Nigra / Q000201:enzymology*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D008070:Lipopolysaccharides; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2