Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA.
Nat Neurosci. 2011 Mar;14(3):357-65. doi: 10.1038/nn.2753. Epub 2011 Feb 6.
Although dystonias are a common group of movement disorders, the mechanisms by which brain dysfunction results in dystonia are not understood. Rapid-onset Dystonia-Parkinsonism (RDP) is a hereditary dystonia caused by mutations in the ATP1A3 gene. Affected individuals can be free of symptoms for years, but rapidly develop persistent dystonia and Parkinsonism-like symptoms after a stressful experience. Using a mouse model, we found that an adverse interaction between the cerebellum and basal ganglia can account for the symptoms of these individuals. The primary instigator of dystonia was the cerebellum, whose aberrant activity altered basal ganglia function, which in turn caused dystonia. This adverse interaction between the cerebellum and basal ganglia was mediated through a di-synaptic thalamic pathway that, when severed, alleviated dystonia. Our results provide a unifying hypothesis for the involvement of cerebellum and basal ganglia in the generation of dystonia and suggest therapeutic strategies for the treatment of RDP.
虽然肌张力障碍是一组常见的运动障碍，但导致肌张力障碍的大脑功能障碍机制尚不清楚。快速发作性肌张力障碍-帕金森病（RDP）是一种遗传性肌张力障碍，由 ATP1A3 基因突变引起。受影响的个体可能多年无症状，但在经历压力后会迅速出现持续的肌张力障碍和帕金森样症状。使用小鼠模型，我们发现小脑和基底神经节之间的不良相互作用可以解释这些个体的症状。肌张力障碍的主要引发因素是小脑，其异常活动改变了基底神经节的功能，进而导致肌张力障碍。小脑和基底神经节之间的这种不良相互作用是通过一个双突触丘脑通路介导的，当该通路被切断时，肌张力障碍得到缓解。我们的研究结果为小脑和基底神经节在肌张力障碍发生中的作用提供了一个统一的假说，并为 RDP 的治疗提供了治疗策略。
