Experimental study on the relationship between levodopa ⁃induced dyskinesia and phosphorylation of ERK in the striatum

Abstract

Objective To explore the relationship between levodopa⁃induced dyskinesia (LID) and phosphorylated extracellular signal ⁃ regulated kinase (ERK, Thr202/Tyr204, ERK1/2) in striatum. Methods The hemiparkinsonian rat model was produced by stereotaxically injecting 6⁃hydroxydopamine (6⁃ OHDA) to right medial forebrain bundle (MFB). The hemiparkinsonian rats were intraperitoneally treated with levodopa (50 mg/kg) and benserazide (12.50 mg/kg) for 21 d and abnormal involuntary movement was evaluated. Immunofluorescent and Western blotting were used to observe the changes of phosphorylation of ERK1/2 in rat's striatum. Results Western blotting indicated that the 6 ⁃ OHDA lesion induced a significant downregulation of the phosphorylation of ERK1/2 to (68.28 ± 7.42)% in comparison with the sham⁃lesioned group [ (107.05 ± 3.81)% ; t = 0.109, P = 0.018]. Chronic treatment with levodopa significantly increased the phosphorylation of ERK1/2 to (160.37 ± 10.54)% , which was compared to the Parkinson's disease (PD) group (t = 0.109, P = 0.000). The study of immunofluorescent staining revealed that there were few phosphorylation of ERK1/2 in the lesion side of hemiparkinsonian rats, and most of them were expressed in dynorphin ⁃ negative neurons; levodopa administration increased the phosphorylation of ERK1/2 expression compared with the PD group (t = 5.121, P = 0.000), and the co⁃expression of the phosphorylation of ERK1/2 and dynorphin increased to (83.62 ± 1.46)％ compared with PD group (t = 11.263, P = 0.003). Conclusion These results suggest that the changes of ERK1/2 phosphorylation state in the strionigral neurons can play an important role in the over ⁃ excitation of the direct pathway medium⁃spiny neurons. DOI：10.3969/j.issn.1672-6731.2011.01.013

Keywords

• Parkinson disease
• Dyskinesia, drug ⁃ induced
• Protein kinases
• Fluorescent antibody technique
• Levodopa