慢性左旋多巴治疗对帕金森病大鼠行为及基底节Fos表达的影响  

Effect of levodopa chronic administration on behavior and Fos expression in the basal ganglia of the PD-rat model

作　　者：徐岩[1] 孙圣刚[1] 曹学兵[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院神经科,湖北武汉430022

出　　处：《中国神经科学杂志》2003年第6期389-394,共6页

基　　金：国家自然科学基金资助项目 (3 0 3 0 0 114 )

摘　　要：目的 :研究帕金森病大鼠左旋多巴诱导异动症模型的行为学特征及其基底节区神经元活性的变化。 方法 :帕金森病大鼠给予左旋多巴治疗 2 8d ,观察其行为学 ,并用免疫组织化学方法观察纹状体、苍白球区Fos表达情况。 结果 :慢性左旋多巴治疗后 ,帕金森病大鼠出现异常不自主运动 ,包括刻板运动和增加的对侧旋转行为。急性左旋多巴治疗帕金森病大鼠损毁侧尾壳核和苍白球区Fos表达均增加 ,慢性左旋多巴治疗与急性治疗组比较损毁侧尾壳核区Fos明显减少 ,而苍白球区表达增加。结论 :慢性间断性左旋多巴治疗诱导帕金森病大鼠异常不自主运动是帕金森病患者左旋多巴诱导异动症的啮齿类动物模型 ,纹状体苍白球神经元活性增强可能参与其发生机制。Objective:To study behavioral characterization and changes of Fos expression in the basal ganglia of rat model of levodopa-induced dyskinesia. Methods: Unilateral 6-hydroxydopamine lesioned rat model of Parkinson disease was established and treated with levodopa /benserazide twice daily for 4 weeks. The behavior changes were observed on the 1,3,5,7,9,10,14,21 and 28 d. Then the rats were sacrificed and immunohistochemical technique was used to detect changes of Fos expression in the caudate putamen(CPU) and globus pallidus(GP) 2 h after the last treatment. Results: Pulsatile treatment with a subthreshold dose of levodopa gradually induced abnormal involuntary movement (AIM),including stereotypy (limb dyskinesia,axial dystonia and masticatory dyskinesia) towards the side contralateral to the dopamine-denervated striatum and increased contraversive rotation. The motor pattern of each subtype was highly stereotypic and the proportion of each subtype was different in individual rat. Fos positive nuclei in the CPU and GP were increased by levodopa acute administration,and more remarkably in the CPU. After repeated levodopa treatment,Fos positive nuclei were reduced remarkably in the CPU,but increased in the GP. Conclusion: The neural mechanism underlying levodopa induced AIM in rat model of PD is very similar to that in levodopa-induced dyskinesia (LID) in PD patients. Increased striatopallidal neuronal activity may be involved in the formation of LID.

关 键 词：慢性左旋多巴 治疗 帕金森病 大鼠 Fos 行为学特征 基底节 神经元活性 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R971[医药卫生—临床医学]