Relationship between motor complications of Parkinson's disease and phosphorylated GluR1Ser845 / 中华神经科杂志

ABSTRACT

Objective To explore the relationship between motor complications of Parkinson's disease(PD)with chronic L-dopa treatment and striatal phosphorylated GluR1Ser845.Methods The hemi-parkinsonian rat model was produced by injecting stereotaxically 6-OHDA to right medial forebrain bundle(MFB).Then the hemi-parkinsonian rat was treated intraperitoneally with L-dopa methylester(25 mg?kg-1?d-1,twice one day)for 22 days and rotational duration and frequency of off period were respectively estimated.After they were sacrificed,their subcellualr distribution of GluR1 and GluR1Ser845 phosphorylation was observed with immunofluorescence and Western blot.Results After the chronic treatment with L-dopa methylester,PD rats displayed shortened rotational duration and increased frequency of off period,which was similar to fluctuations of the symptoms and on-off phenomenon in PD patients.In the lesioned striatum of PD rats,the amount of GluR1 and phosphorylated GluR1Ser845 in striatal membrane was reduced to 73.0%?4.8% and 42.0%?5.6%,respectively,compared with those non-lesioned.After chronic treatment of PD rats with L-dopa,the amount of GluR1 and phosphorylated GluR1Ser845 in striatal membranes were increased to 104.0%?5.5% and 112.0%?3.4%.These unique changes occurred only in parvalbumin-positive interneurons.Conclusions These findings suggest that subcellular distribution and phosphorylation state of GluR1Ser845 in parvalbumin-positive interneurons may play a significant role in the pathogenesis of motor complications of chronic L-dopa treatment for PD.