OBJECTIVETo investigate the effect of phosphorylated-ERK1/2 (p-ERK1/2) on inducible nitric oxide synthase (iNOS) expression in the substantia nigra (SN) of a mouse model of Parkinson's disease (PD), and explore the possible mechanism of dopaminergic (DA) neuron loss in the SN of the midbrain in PD.

METHODSPD was induced by intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) in C57BL/6N mice, and the behavioral changes of the PD mouse model were observed. Immunohistochemistry and Western blotting were used to detect the number of positive cells and the expressions of tyrosine hydroxylase (TH), p-ERK1/2 and iNOS in the SN of the PD mice, and their changes following Rg1 treatment were assessed.

RESULTSThe PD mice exhibited typical symptoms of PD, in which the number of TH-positive neurons and TH expression were significantly reduced by about 77% and 75% (P<0.01), respectively, 7 days after the 5th injection of MPTP as compared with those in the control group. Rg1 pretreatment significantly decreased the number of TH-positive neurons and TH expression by 44% and 41% (P<0.01), respectively. p-ERK1/2 expression was not observed in the cell nuclei until 1.5 h after the third injection of MPTP, and increased markedly at 6 h. Rg1 pretreatment significantly inhibited the expression of p-ERK1/2 and iNOS (P<0.01). A significant positive correlation was noted between the expression of p-ERK1/2 and iNOS (P<0.01).

CONCLUSIONP-ERK1/2 may regulate the expression of iNOS to induce DA neuron loss in the SN of PD, and Rg1 may protect the DA neurons possibly by depressing nuclear translocation of P-ERK1/2.