Cyclooxygenases mRNA and protein expression in striata in the experimental mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration to mouse.

Cyclooxygenases (COX) are associated with complex alteration in many pathologies of the central nervous system (CNS). Increased expression of COX-2 has been shown in injured or degenerated neurons, thus suggesting that COX-2 may contribute to neuronal damage. In this study, we present the expression of COX-1 and COX-2 mRNA and protein in striatum following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration to mice. MPTP causes an acute damage of dopaminergic neurons especially in the nigrostriatal dopaminergic system, thus diminishing dopamine (DA) content in striatum and decreasing the number of dopaminergic cells in the pars compacta of the substantia nigra (SN). C57Bl mice have received 60 mg/kg of MPTP introperitoneally. A group of mice received also rofecoxib 10 mg/kg from the 1st day following MPTP administration. Dopamine content in striatum (high-performance liquid chromatography-HPLC), mRNA expression of COX-1 and -2 (reverse transcriptase-polymerase chain reaction technique-RT-PCR), COX-1 and -2 protein content (immunoblotting) have been measured on day 1st, 3rd, 7th, 14th and 21st after the injury. We have found that COX-1 mRNA expression is not changed following MPTP administration, but COX-2 gene and protein expression in striatum increases from the 3rd to the 7th and 14th days, and diminishes on the 21st day. Production of prostaglandins is augmented only briefly after MPTP treatment and did not correlate with increased COX-2 mRNA and COX-2 protein production. Thus, the increase of COX-2 expression does not follow the acute stage of cell death but rather the recovery period after the injury. We also demonstrate that COX-2 activity inhibition by rofecoxib (10 mg/kg), which has been started 1 day after the injury, has not neuroprotective effect. Our study suggests that COX-2 does not contribute to neurons death following MPTP administration and that the inhibition of COX-2 activity is not beneficial to neurons injured by MPTP. However, COX-2 mRNA and protein expressions increase after MPTP injury; the role of these findings remains obscure.