皮层电刺激对左旋多巴诱发异动症大鼠纹状体c-fos及ENK表达的影响

为了研究皮层电刺激对左旋多巴诱发异动症(LID)大鼠纹状体神经元c-fos及脑啡肽(ENK)表达的影响,探讨皮层-纹状体通路可塑性改变在LID发生机制中的作用,本实验制备Parkinson病(PD)和LID大鼠模型,将实验大鼠分成三组:正常对照组、PD组和LID组。电刺激运动皮层后,免疫组化法检测纹状体区c-fos、ENK、细胞外信号调节激酶1/2(ERK1/2)及其活化形式磷酸化细胞外信号调节激酶1/2(p-ERK1/2)的表达。结果显示:与对侧比较,皮层电刺激使各组同侧纹状体c-fos、ENK、ERK1/2、p-ERK1/2表达均增加(P<0.01);LID组c-fos(0.67±0.03)以及p-ERK1/2的表达(0.17±0.05)较PD组(0.08±0.03)和正常组(0.07±0.02)增加(P<0.05),LID组ENK(0.21±0.07)的表达和PD组(0.18±0.08)相比较无统计学差异(P>0.05),但均较正常组(0.08±0.01)增加(P<0.01);三组ERK1/2的表达无统计学差异(P>0.05),但LID组p-ERK1/2的表达(0.17±0.05)较PD组和正常组有所增加(P<0.01)。本研究结果表明,LID大鼠皮层-纹状体通路兴奋使纹状体c-fos以及p-ERK1/2表达增加,ENK的表达没有显著变化。上述结果提示皮层-纹状体通路活动增强以及p-ERK1/2表达的增加与LID的发生机制有关,而ENK在LID的发生过程中可能不发挥重要作用。

The effect of the cortical electrical stimulation on the expression of the c-fos and ENK in striatal neurons of rats with levodopa-induced dyskinesia

In order to study the effect of the cortical electrical stimulation on the expression of the c-fos and ENK in striatal neurons of rots with levedopa-induced dyskinesia (LID) and to understand the plasticity of corticostriatal pathway in the pathogenesis of LID, Parkinson' s disease (PD) and LID rat models were made. The successful models and other normal rats were divided into three groups: normal control group, PD group. LID group, After electric stimulation of the motor cortex, the rats were executed and processed for examining c-fos, en-kephalin (ENK), extracellular regulated kinase 1/2 (ERK1/2) and phosphorylated-ERK1/2 (p-ERK1/2) in striatum using immunohis-tachemistry. The results showed that, compared with the contralateral side, the expression of the c-fos, ENK, ERK1/2 and p-ERK1/2 in ipsilatend striatum in each group increased significantly (P<0.01). LID rats expressed more c-los (0.67±0.03) and p-ERK1/2 (0. 17 ±0.05) than both of PD rats (0.08 ±0.03) and normal rats (0.07 ±0.02) (P<0.05). ENK expressional level in LID group (0.21 ± 0.07) was not significantly different from that of the PD group (0. 18 ±0. 08) (P >0. 05), but stronger than that of the normal group (0.08 ±0.01) (P <0.01). The expression of ERK1/2 in three groups was equal (P >0.05), but the p-ERK1/2 expressional level in LID rats (0.17 ± 0. 05) was significantly higher than that of the other two groups (P <0. 01). These results suggest that the excited corti-costriatal pathway of LID rats induced high-levels of c-fos, accompanied by increased phesphorylation of the ERK but not enkephalin, indi-cating that the enhanced activity of the corticostriatal pathway and the phosphorylation of the ERK are involved in the pathogenesis of LID, and ENK may not play important roles in the developmental medehanism of LID.