Chen Zhibin, Guan Qiang, Cao Xuebing, Xu Yan, Wang Lan, Sun Shenggang
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
J Huazhong Univ Sci Technolog Med Sci. 2006;26(5):542-4. doi: 10.1007/s11596-006-0514-7.
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.
探讨反义FosB和环磷酸腺苷反应元件结合蛋白（CREB）纹状体内注射对帕金森病（PD）左旋多巴诱导的异动症（LID）大鼠纹状体神经元中前强啡肽原（PDyn）基因表达的影响。通过立体定向注射6-羟基多巴胺建立大鼠PD模型。大鼠经腹腔慢性间歇性注射左旋多巴28天以获得LID大鼠。将反义FosB和CREB分别注射到所有大鼠的纹状体中。采用原位杂交法检测纹状体中PDyn mRNA表达的变化，并观察行为变化。结果显示，与正义FosB组相比，注射反义FosB后，LID大鼠的异常不自主运动（AIM）减少，纹状体中PDyn mRNA的表达增加（P均<0.01）。与对照组相比，反义CREB处理的LID组纹状体中PDyn mRNA的表达降低（P<0.01），与正义CREB处理的LID组相比，反义CREB处理的LID组AIM评分和PDyn mRNA的表达均无变化（P均>0.05）。综上所述，取代CREG的FosB蛋白可调节PDyn mRNA的表达，并在LID的发病机制中起关键作用。
