Effect of antisense FosB and CREB on the expression of prodynorphin gene in rats with levodopa-induced dyskinesias.
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.
Chen
Zhibin
Z
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Guan
Qiang
Q
Cao
Xuebing
X
Xu
Yan
Y
Wang
Lan
L
Sun
Shenggang
S
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000494:pharmacology*; D004409:Dyskinesia, Drug-Induced / Q000235:genetics* / Q000378:metabolism; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D009474:Neurons / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D017362:Cyclic AMP Response Element-Binding Protein; D004745:Enkephalins; C483820:Fosb protein, rat; D016376:Oligonucleotides, Antisense; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D007980:Levodopa; C033660:preproenkephalin