Effects of ERK1/2 signal pathway on COX-2,PGE2 expression in subacute MPTP-induced mouse model of Parkinson's disease

AIM:To investigate effects of ERK1/2 signaling pathway on the expression of Cyclooxygenase-2(COX-2)and Prostaglandin E2(PGE2)in substantia nigra(SN)of the mouse model of Parkinson's disease(PD)induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)and to further explore the possible mechanism of dopaminergic neurons loss in PD.METHODS:C57BL/6 mice were administrated with MPTP to produce the subacute PD model,and the mice were observed the behavioral changes.Immunohistochemistry and Western Blot for tyrosine hydroxylase(TH),cyclooxygenase-2(COX-2),prostaglandin E2(PGE2)and phosphorylated ERK1/2(p-ERK1/2)were used to observe the changes of positive cell number in SN.After treatment with U0126,a specific inhibitor of ERK,the changes of above-mentioned indices were also observed.RESULTS:Compared with the mice in control group,the mice model appears typical of PD-like symptoms.P-ERK1/2-positive cells increased significantly at 1h after the 3rd injection of MPTP.The number of COX-2-,PGE2-positive cells was increased obviously as compared with the control group at 24 h after the 5th injection of MPTP.TH-positive neurons in the PD model group were substantially reduced by about 50%.Treated with U0126,a specific inhibitor of ERK,the performance of PD-like symptoms mitigated,the expression level of p-ERK1/2,COX-2 and PGE2 were significantly decreased in SN compared with mice model group.The number of TH-positive cells in the SN was decreased by only 25% at 24 h after the 5th injection of MPTP.CONCLUSION:ERK1/2 signal pathway may play an important role in regulating COX-2 and PGE2 expression in SN in the early stage of MPTP-induced subacute PD,and inhibition of ERK1/2 signal pathway activity may provide neuroprotective effects for DA neurons in the PD mouse model.