Touchon Justin C, Moore Cynthia, Frederickson Julie, Meshul Charles K
Research Services, Neurocytology Laboratory, VA Medical Center, Portland, Oregon 97239, USA.
Synapse. 2004 Mar 15;51(4):287-98. doi: 10.1002/syn.10306.
A unilateral lesion of the rat nigrostriatal pathway with 6-hydroxydopamine (6-OHDA) results in a decrease in the basal extracellular level of striatal glutamate, a nearly complete loss of tyrosine hydroxylase (TH) immunolabeling, an increase in the density of glutamate immunogold labeling within nerve terminals making an asymmetrical synaptic contact, and an increase in the number of apomorphine-induced contralateral rotations. [Meshul et al. (1999) Neuroscience 88:1-16; Meshul and Allen (2000) Synapse 36:129-142]. In Parkinson's disease, a lesion of either the subthalamic nucleus (STN) or the motor thalamic nucleus relieves the patient of some of the motor difficulties associated with this disorder. In this rodent model, either the STN or motor thalamic nucleus was electrolytically destroyed 2 months following a unilateral 6-OHDA lesions. Following a lesion of either the STN or motor thalamic nucleus in 6-OHDA-treated rats, there was a significant decrease (40-60%) in the number of apomorphine-induced contralateral rotations compared to the 6-OHDA group. There was a significant decrease (<30%) in the basal extracellular level of striatal glutamate in all of the experimental groups compared to the sham group. Following an STN and/or 6-OHDA lesion, the decrease in striatal extracellular levels was inversely associated with an increase in the density of nerve terminal glutamate immunolabeling. There was no change in nerve terminal glutamate immunogold labeling in either the motor thalamic or motor thalamic plus 6-OHDA lesion groups compared to the sham group. The decrease in the number of apomorphine-induced rotations was not due to an increase in TH immunolabeling (i.e., sprouting) within the denervated striatum. This suggests that alterations in striatal glutamate appear not to be directly involved in the STN or motor thalamic lesion-induced reduction in contralateral rotations.
用6-羟基多巴胺（6-OHDA）对大鼠黑质纹状体通路进行单侧损伤，会导致纹状体谷氨酸的基础细胞外水平降低、酪氨酸羟化酶（TH）免疫标记几乎完全丧失、在形成不对称突触联系的神经终末内谷氨酸免疫金标记密度增加，以及阿扑吗啡诱导的对侧旋转次数增加。[Meshul等人（1999年），《神经科学》88:1-16；Meshul和Allen（2000年），《突触》36:129-142]。在帕金森病中，损毁丘脑底核（STN）或运动丘脑核可使患者的一些与该疾病相关的运动困难得到缓解。在这个啮齿动物模型中，在单侧6-OHDA损伤2个月后，对STN或运动丘脑核进行电解损毁。在6-OHDA处理的大鼠中，损毁STN或运动丘脑核后，与6-OHDA组相比，阿扑吗啡诱导的对侧旋转次数显著减少（40-60%）。与假手术组相比，所有实验组纹状体谷氨酸的基础细胞外水平均显著降低（<30%）。在STN和/或6-OHDA损伤后，纹状体细胞外水平的降低与神经终末谷氨酸免疫标记密度的增加呈负相关。与假手术组相比，运动丘脑或运动丘脑加6-OHDA损伤组的神经终末谷氨酸免疫金标记没有变化。阿扑吗啡诱导的旋转次数减少并非由于去神经支配的纹状体内TH免疫标记增加（即发芽）。这表明纹状体谷氨酸的改变似乎并非直接参与STN或运动丘脑损伤诱导的对侧旋转减少。
