Experimental study on the role of externally regulated kinase pathway in the pathogenesis of parkinsonism related motor complications / 中华神经科杂志

ABSTRACT

Objective To investigate the role of externally regulated kinase (ERK) in a rat model of levodopa-induced motor complications. Methods The hemi-parkinsonian rat model was produced by injecting stereotaxically 6-OHDA to right medial forebrain bundle(MFB). First, rats were intraperitoneally treated with levodopa (50 mg/kg with benserazide 12.5 mg/kg, twice daily) for 22 days. On day 23, rats were treated with ERK inhibitor, PD98059 before levodopa administration. Rotational duration and peak rotation were estimated. After sacrificed, ERK1/2 phosphorylation was observed by Western blot. Results Our study showed that chronic treatment of lesioned rats with levodopa markedly upregulated the ERK1/2 phosphorylation of in lesioned striatum(155.6%±6.5%). PD98059 could reduce hyperphosphorylation of ERK1/2(85.4%±5.6%). Meanwhile, PD98059 reversed both the shortened rotational duration and increased peak rotation induced by chronic levodopa treatment. Moreover, PKC inhibitor could partly downregulated the ERK1/2 phosphorylation(101.2%±6.2%, compared with levodopa+vehide, t=3.2, P<0.05). Conclusions These results indicated that the development of motor complications could be associated with activation of ERK pathway. And more, activation of ERK was partly dependent on PKC. Pharmaceuticals which act to inhibit ERK pathway may be useful in the treatment of parkinsonism related motor complications.