Kim Dohee, Jeon Jeha, Cheong Eunji, Kim Dong Jin, Ryu Hoon, Seo Hyemyung, Kim Yun Kyung
Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul, 136-791, South Korea.
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, South Korea.
Mol Neurobiol. 2016 May;53(4):2276-86. doi: 10.1007/s12035-015-9214-2. Epub 2015 May 15.
Huntington's disease (HD) is a movement disorder characterized by the early selective degeneration of striatum. For motor control, the striatum receives excitatory inputs from multiple brain regions and projects the information to other basal ganglia nuclei. Despite the pathological importance of the striatal degeneration in HD, there are little anatomical data that show impaired striatal connectivity in HD. For the anatomical mapping of the striatum, we injected here a neurotracer DiD to the dorsal striatum of HD mouse model (YAC128). Compared with littermate controls, the number of the traced inputs to the striatum was reduced dramatically in YAC128 mice at 12 months of age suggesting massive destruction of the striatal connections. Basal ganglia inputs were significantly damaged in HD mice by showing 61 % decrease in substantia nigra pars compacta, 85% decrease in thalamic centromedian nucleus, and 55% decrease in thalamic parafascicular nucleus. Cortical inputs were also greatly decreased by 43% in motor cortex, 48% in somatosensory cortex, and 72% in visual cortex. Besides the known striatal connections, the neurotracer DiD also traced inputs from amygdala and the amygdala inputs were decreased by 68% in YAC128 mice. Considering the role of amygdala in emotion processing, the impairment in amygdalostriatal connectivity strongly suggests that emotional disturbances could occur in HD mice. Indeed, open-field tests further indicated that YAC128 mice exhibited changes in emotional behaviors related to symptoms of depression and anxiety. Although onset of HD is clinically determined on the basis of motor abnormality, emotional deficits are also common features of the disease. Therefore, our anatomical connectivity mapping of the striatum provides a new insight to interpret brain dysfunction in HD.
亨廷顿舞蹈症（HD）是一种运动障碍疾病，其特征为纹状体早期选择性退化。对于运动控制而言，纹状体接收来自多个脑区的兴奋性输入，并将信息投射至其他基底神经节核团。尽管纹状体退化在HD中具有病理学重要性，但几乎没有解剖学数据表明HD患者存在纹状体连接受损的情况。为了对纹状体进行解剖学映射，我们在此向HD小鼠模型（YAC128）的背侧纹状体注射了神经示踪剂DiD。与同窝对照相比，12月龄的YAC128小鼠中，纹状体的示踪输入数量显著减少，这表明纹状体连接遭到了大量破坏。黑质致密部减少了61%、丘脑中央中核减少了85%、丘脑束旁核减少了55%，这些数据表明HD小鼠的基底神经节输入受到了显著损害。运动皮层减少了43%、体感皮层减少了48%、视觉皮层减少了72%，这表明皮层输入也大幅减少。除了已知的纹状体连接外，神经示踪剂DiD还追踪到了来自杏仁核的输入，在YAC128小鼠中，杏仁核输入减少了68%。考虑到杏仁核在情绪处理中的作用，杏仁核 - 纹状体连接受损强烈表明HD小鼠可能会出现情绪障碍。事实上，旷场试验进一步表明，YAC128小鼠表现出与抑郁和焦虑症状相关的情绪行为变化。虽然HD的发病在临床上是根据运动异常来判定的，但情绪缺陷也是该疾病的常见特征。因此，我们对纹状体的解剖连接映射为解释HD患者的脑功能障碍提供了新的见解。
