The Role Of Δ FosB Overexpression In The Development Of Dyskinesia In PD Rats And The Study On Its Gene Targets

Objective To study the role of striatalΔFosB in the development of dyskinesia in PD rats and the influence on the expression of NR1,GluR1 and NF-κB mRNA.Methods The hemiparkinsonian rat model was established by 6-OHDA injection stereotaxically to the left medial forebrain bundle(MFB).Then they received single injection of levodopa and benserazide intraperitoneally to detect the recation of the drugs.The rats were divided randomly into experimental group and control group.The rats in experimental group and control group were respectively treated to infuse rAAV-ΔFosB-EGFP or rAAV-EGFP stereotaxically to the lesioned side of striatum.Their striatums in the right side were used as unlesioned side group severally. The rats were again divided into four subgroups,they were kept for three weeks,six weeks,nine weeks and twelve weeks respectively.Then all the rats were treated by injecting levodopa and benserazide intraperitoneally one time,dose as before,to indect the behavioral changes in the different subgroups.The levels ofΔFosB were measured by immunohistochemistry and the levels of NR1,GluR1 and NF-κB mRNA were detected by real-time PCR technology.Results None of the rats in either group displayed abnormal involuntary movements(AIMs) before the viral injection. In experimental group :All the rats showed AIMs after drugs treatment and the overexpression ofΔFosB in the lesioned side of striatum were discovered.As time increased, the AIM scores were increased generally(P<0.01 ) ,the levels ofΔFosB,NR1 and NF-κB mRNA increased gradually.In the same week, the levels ofΔFosB,NR1 and NF-κB mRNA in the experimental group were both higher than that in the control group in lesioned side of striatum and that in the unlesioned side groups (both P<0.05 ).In the control group , the levels ofΔFosB and NF-κB mRNA in lesioned side of striatum were also higher than that in unlesioned side of striatum (P<0.05 ). However, there were no differences of GluR1 mRNA in both striatums in the experimental and control groups(P>0.05 ).Conclusions rAAV-ΔFosB-EGFP injection to the lesioned side of striatum in PD rats can simulate the occurrence of dyskinesia;Striatal overexpression ofΔFosB may relate to the development of dyskinesia in PD rats by regulating genes (NR1 and NF-κB).