左旋多巴诱发异动症大鼠皮质纹状体突触超微结构与功能的变化  

Study on corticostriatal synapse ultrastructure and function in rats with levodopa induced dyskinesias

作　　者：曹学兵[1] 孙圣刚[1] 王岚[1] 徐岩[1] 童萼塘[1] 袁光雷[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,武汉430022

出　　处：《中华神经科杂志》2004年第2期126-130,共5页Chinese Journal of Neurology

基　　金：国家自然科学基金资助项目 ( 3 0 3 0 0 114 )

摘　　要：目的　探讨左旋多巴诱发异动症 (levodopainduceddyskinesias ,LID)大鼠皮质纹状体突触结构和功能的变化。方法　 6 羟多巴胺 (6 OHDA)立体定位注射制备偏侧帕金森病 (Parkinsondisease,PD)大鼠模型 ,复方左旋多巴 (L dopa)甲酯腹腔注射治疗 4周 (2 0mg·kg-1·d-1,每天 2次 )诱发LID大鼠模型。采用免疫组化及透射电镜方法对大鼠皮质纹状体突触界面的结构进行定量分析 ,并观察单次地佐环平 (MK 80 1,0 1mg/kg)治疗后突触前谷氨酸 (Glu)释放量的变化。结果　透射电镜证实皮质Glu能纤维与纹状体神经元的树突棘构成不对称突触 ,与PD大鼠比较 ,LID大鼠Glu能非对称性突触中穿孔性突触进一步增加 (P <0 0 1) ,且突触间隙变窄 ,突触后致密物质 (post synapticdensity ,PSD)厚度增加 (P <0 0 5 )。同时伴有突触前Glu释放量的增多 ,但可被N 甲基 D 门冬氨酸 (NMDA)受体拮抗剂MK 80 1所抑制。结论　慢性L dopa治疗使皮质纹状体突触功能进一步活化 ,其中涉及突触后形态和功能的改变及突触前活性的增强 。Objective To study the corticostriatal synaptic activity, synaptic structural parameters and glutamate releasing in rats with levodopa (L-dopa) induced dyskinesias (LID). Methods Hemiparkinsonian (PD) rats established by 6-OHDA microinjection stereotaxically, were treated with chronic intermitent L-dopa celiac injection for 28 days (20 mg·kg -1 ·d -1 L-dopa methylester and 5.0 mg·kg -1 ·d -1 benserazide twice a day)to get the LID rat models according to their behavioral changes. Immunocytochemistry was used to evaluate glutamate- immunopositive terminals following single dizocilpine (MK-801, 0.1 mg/kg) treatment and the immunoelectron microscopy technique was used for measuring synaptic structure parameters such as the asymmetric synapse cleft width,the post-synapse density depth,and the ratio of perforated synapse,etc. Results Chronic pulsative L-dopa treatment induced the occurrence of dyskinesias in hemiparkinsonian rats. In the subsequent analysis, Glutamate- immunopositive terminals were significantly increased in the striatum both PD and LID groups, especially in the latter (P<0.01),but the single treatment with MK-801 could reverse the increased change. In electron microscopy quantitatively analyzing the asymmetric corticostriatal synapse,post-synapse density depth was much thicker, synapse cleft width was narrower in the LID group as compared with the PD and normal groups (P<0.05). The ratio of perforated synapse increased by degrees in normal,PD and LID groups was 5.08%,9.84%,and 18.21% respectively. Conclusions The glutamate-synapse activity was increased in PD and LID rats and chronic L-dopa treatment made the synapse more active especially in the post-synaptic conformation and the function. The corticostriatal synaptic structural and function changes as a material basis of synaptic plasticity might play an important role in the pathogenesis of LID.

关 键 词：左旋多巴 异动症 大鼠 皮质纹状体 LID 突触 超微结构 6一羟多巴胺 6-OHDA 帕金森病 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]