Comprehensive study on dystonia pathology

在哺乳动物纹状体中，存在两种功能细分，称为纹状体室和基质室。我们提出了一个假设，即纹状体和基质室之间的不平衡活动可能导致包括肌张力障碍在内的运动障碍。在过去的3年里，我们发现在肌张力障碍转基因小鼠模型中，纹状体中多巴胺D1受体D1R和Golf表达的选择性缺失，提示纹状体中D1R介导的信号缺失可能导致肌张力障碍症状。此外，我们对尸检脑的病理研究显示DYT3肌张力障碍患者纹状体神经肽NPY系统存在缺陷。由于NPY对谷氨酸受体介导的神经毒性具有保护作用，并促进纹状体神经发生，这一发现表明NPY系统的缺陷可能是主要发生在纹状体室的进行性纹状体生成的基础。

In the mammalian striatum, there exist two functional subdivisions termed as striosome and matrix compartments. We have proposed a hypothesis that an imbalanced activities between the striosome and matrix compartments may cause movement disorders that include dystonia. During the last 3 years, we found a selective loss of dopamine D1 receptor D1R and Golf expression in the striosomes in a transgenic mouse model with dystonia, and suggest that a loss of D1Rmediated signaling in the striosomes may cause dystonia symptoms. Moreover, our pathological study on the autopsied brains showed the defects in the neuropeptide NPY system in the striatum of the patients with DYT3 dystonia. Since NPY has a protective role against glutamate receptor-mediated neurotoxicity and promotes striatal neurogenesis, this finding suggests that defects in the NPY system may underlie the genesis of progressive striatal generation that primarily occurs in the striosome compartment.