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 1 h 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 5 th 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.
NETL
NSTL
万方数据
维普
