Effect of antisense FosB and CREB on the expression of prodynorphin gene in rats with Levodopa-induced dyskinesias

Abstract

The effects of antisense FosB and CREB intra-striatum injection on the expression of prodynorphin (PDyn) gene in striatal neurons of Levodopa-induced dyskinesias (LID) rats with Parkinson disease (PD) were explored. PD model in rats was established by 6-OHDA microinjection stereotaxically. The rats were treated with chronic intermittent Levodopa celiac injection for 28 days to get the LID rats. Antisense FosB and cAMP response element-binding protein (CREB) were injected into striatum of all rats respectively. In situ hybridization was used to measure the changes in the expression of PDyn mRNA in striatum and behavior changes were observed. The results showed after administration of antisense FosB, abnormal involuntary movement (AIM) was decreased and the expression of PDyn mRNA in striatum was increased in LID rats as compared with sense FosB group (P<0.01, respectively). As compared with the control group, the expression of PDyn mRNA in striatum was decreased by antisense CREB-treated LID group (P<0.01) and compared with sense CREB treated LID group, antisense CREB-treated LID group showed no changes in AIM scores and the expressions of PDyn mRNA (both P>0.05). In conclusion, FosB protein, which replaced the CREG, could regulate the expression of PDyn mRNA and play critical role in the pathogenesis of LID.

Keywords

Levodopa-induced dyskinesias / Levodopa / Parkinson’s disease / antisense oligonucleotide

References

[1] BrotchieJ. M., LeeJ., VenderovaK.. Levodopa-induced dyskinesia in Parkinson’s disease. J Neural Transm, 2005, 112: 359-391

[2] CaoX. B., SunS. G., WangL., et al.. Study on corticostriatal synapse ultrastructure and function in rats with Levodopa induced dyskinesias. Chin J Neurol, 2004, 7(2): 126-130

[3] AnderssonM., WestinJ. E., CenciM. A.. Time course of striatal DeltaFosB-like immunoreactivity and prodynorphin mRNA levels after discontinuation of chronic dopaminomimetic treatment. Eur J Neurosci, 2003, 17(3): 661-666

[4] DoucetJ. P., NakabeppuY., BedardP. J., et al.. Chronic alterations in dopaminergic neurotransmission produce a persistent elevation of deltaFosB-like protein(s) in both the rodent and primate striatum. Eur J Neurosci, 1996, 8: 365-381

[5] ZhangL., LouD., JiaoH., et al.. Cocaine-induced intracellular signaling and gene expression are oppositely regulated by the dopamine D1 and D3 receptors. J Neurosci, 2004, 24(13): 3344-3354