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.

• Authors: Zhibin Chen, Qiang Guan, Xuebing Cao, Yan Xu, Lan Wang, Shenggang Sun
• Journal: Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban (J Huazhong Univ Sci Technolog Med Sci) Vol. 26 Issue 5 Pg. 542-4 ( 2006) ISSN: 1672-0733 [Print] China
• PMID: 17219962 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclic AMP Response Element-Binding Protein
• Enkephalins
• Fosb protein, rat
• Oligonucleotides, Antisense
• Protein Precursors
• Proto-Oncogene Proteins c-fos
• RNA, Messenger
• Levodopa
• preproenkephalin

Topics

• Animals
• Corpus Striatum (metabolism)
• Cyclic AMP Response Element-Binding Protein (pharmacology)
• Dyskinesia, Drug-Induced (genetics, metabolism)
• Enkephalins (genetics, metabolism)
• Female
• Levodopa (adverse effects, therapeutic use)
• Neurons (metabolism)
• Oligonucleotides, Antisense (pharmacology)
• Parkinson Disease (drug therapy)
• Protein Precursors (genetics, metabolism)
• Proto-Oncogene Proteins c-fos (pharmacology)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley