Effect of phosphorylated c-Jun expression on COX-2 expression in the substantia nigra of MPTP mouse model of subacute Parkinson disease

Objective To investigate the effect of phophorylated c-Jun(p-c-Jun)expression on the expression of COX-2 in the substantia nigra(SN)of the MPTP mouse model of subacute Parkinson disease(PD)and explore the possible mechanism of the dopaminergic(DA)neuron death in PD.Methods C57BL/6N mice were treated with MPTP to establish subacute PD model.The changes of TH-,COX-2-and p-c-Jun-positive cells,and the expression levels of TH,COX-2 and p-c-Jun in the SN in the midbrain were observed with inmmunohistochemistry and Western blotting before and after administration of SP600125,a specific JNK inhibitor.Results Compared with the mice in control group,the PD mice exhibited typical symptoms of PD.The number of TH-positive neurons and expression level of TH in the model group were significantly reduced in the substantia nigra by about 65% and 75%(P0.001)7 days after the fifth injection of MPTP.The number of COX-2-immunoreactive cells and the expression level of COX-2 were significantly increased.P-c-Jun was specifically expressed in the nuclei of neurons and p-c-Jun expression level was significantly increased in the SN 6 h after the third injection of MPTP.Double-labeling immunofluorescence assay showed coexpression of COX-2 and p-c-Jun in TH-positive neurons in the SN.In mice treated with JNK inhibitor,the number of TH-positive neurons and TH expression level in the SN was only decreased by 15% and 20% as compared with the control group(P0.001)7 days after the fifth injection of MPTP,COX-2-positive cell number and COX-2 expression level were obviously reduced as compared with the model group(P0.001),and p-c-Jun was expressed mainly in the cytoplasm of the neurons whose expression level in SN were significantly decreased 6 h after the third injection of MPTP.The PD mice treated with SP600125 showed slight behavioral symptoms.Conclusion P-c-Jun expression may play an important role in mediating COX-2 expression in the SN in the MPTP model of subacute PD,and inhibiting p-c-Jun activity may provide neuroprotection to the mouse model.