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【Brain】Dystonia并非只是基底神经节功能异常
The basal ganglia and cerebellum interact in the expression of dystonic movement
Vladimir K. Neychev1,2, Xueliang Fan1, V. I. Mitev2, Ellen J. Hess1,3 and H. A. Jinnah1
1Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA, 2Department of Biochemistry, Medical University of Sofia, Bulgaria and 3Department of Neurosciences, Johns Hopkins University, Baltimore, MD 21287, USA
Correspondence to: H. A. Jinnah, MD, PhD, Department of Neurology, Johns Hopkins University, 600 North Wolfe Street, Baltimore, MD 21287, USA E-mail: hjinnah@jhmi.edu
Dystonia is a neurological disorder characterized by excessive involuntary muscle contractions that lead to twisting movements or abnormal posturing. Traditional views place responsibility for dystonia with dysfunction of basal ganglia circuits, yet recent evidence has pointed towards cerebellar circuits as well. In the current studies we used two strategies to explore the hypothesis that the expression of dystonic movements depends on influences from a motor network that includes both the basal ganglia and cerebellum. The first strategy was to evaluate the consequences of subthreshold lesions of the striatum in two different animal models where dystonic movements are thought to originate from abnormal cerebellar function. The second strategy employed microdialysis to search for changes in striatal dopamine release in these two animal models where the cerebellum has been already implicated. One of the animal models involved tottering mice, which exhibit paroxysmal dystonia due to an inherited defect affecting calcium channels. In keeping with prior results implicating the cerebellum in this model, surgical removal of the cerebellum eliminated their dystonic attacks. In contrast, subclinical lesions of the striatum with either 6-hydroxydopamine (6OHDA) or quinolinic acid (QA) exaggerated their dystonic attacks. Microdialysis of the striatum revealed dystonic attacks in tottering mice to be associated with a significant reduction in extracellular striatal dopamine. The other animal model involved the induction of dystonia via pharmacological excitation of the cerebellar cortex by local application of kainic acid in normal mice. In this model the site of stimulation determines the origin of dystonia in the cerebellum. However, subclinical striatal lesions with either 6OHDA or QA again exaggerated their generalized dystonia. When dystonic movements were triggered by pharmacological stimulation of the cerebellum, microdialysis revealed significant reductions in striatal dopamine release. These results demonstrate important functional relationships between cerebellar and basal ganglia circuits in two different animal models of dystonia. They suggest that expression of dystonic movements depends on influences from both basal ganglia and cerebellum in both models. These results support the hypothesis that dystonia may result from disruption of a motor network involving both the basal ganglia and cerebellum, rather than isolated dysfunction of only one motor system.
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题目：肌张力障碍表达中基底神经节和小脑的交互作用
肌张力障碍是一类以过度的不随意的肌肉收缩并引起异常扭动或异常姿势为特征的神经疾病。传统观点将肌张力障碍归因于基底神经节环路功能的异常，但是新近的研究证据却提示小脑环路也参与其中。在本研究中，我们利用两个策略来求证这种假设，即肌张力障碍性运动的产生依赖于某个运动网络的作用，这一网络既包括基底神经节，也包括小脑。第一个方案为评估两个不同的动物模型纹状体亚临床损伤后的结果，纹状体损伤部位引起的肌张力障碍在损伤前被认为是源于小脑功能的异常。第二个方案采用微量渗析技术研究上述两种小脑已经受累的动物模型纹状体多巴胺释放的变化。其中一种动物模型包括由于遗传性钙通道功能缺失而出现阵发性肌张力障碍的蹒跚鼠。与本模型先前暗示小脑也参与肌张力障碍性运动的判断相一致，手术摘除小脑后这种阵发性肌张力障碍消失了。相反，利用6-羟基多巴胺和喹啉酸引起的纹状体亚临床损伤者增加肌张力障碍性运动的发作。纹状体的微量渗析结果显示蹒跚鼠的肌张力障碍发作与细胞外纹状体多巴胺水平下降显著相关。另一组动物模型为正常小鼠在小脑皮层局部应用红藻氨酸，通过药物刺激作用诱发的肌张力障碍。此模型中刺激的位点决定肌张力障碍的起源。然而，通过6-羟基多巴胺和喹啉酸造成的纹状体亚临床损伤再次增加肌张力障碍的全面发作。当肌张力障碍是由于药物刺激小脑而触发时，微量渗析显示纹状体多巴胺释放显著减少。上述结果证实了不同肌张力障碍动物模型中小脑和基底神经节环路之间的重要功能关系。这说明在两种动物模型中，肌张力障碍的表达受到基底神经节和小脑的共同影响。研究结果支持前述假说，即肌张力障碍是由于涉及基底神经节和小脑两者的一个运动网络功能障碍所致，而不是其中某一系统单独的功能障碍。[标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-07-09 12:04
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