Effect of phosphorylated c-Jun expression on COX-2 expression in the substantia nigra of MPTP mouse model of subacute Parkinson disease / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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% (P<0.001) 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 (P<0.001) 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 (P<0.001), 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.</p><p><b>CONCLUSION</b>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.</p>