Department of Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
Neuroscience. 2013 May 15;238:71-81. doi: 10.1016/j.neuroscience.2013.01.071. Epub 2013 Feb 9.
The predominant motor symptom in Huntington's disease (HD) is chorea. The patho-anatomical basis for the chorea is not well known, but a link with the dopaminergic system has been suggested by post-mortem and clinical studies. Our previous work revealed an increased number of dopamine-containing cells in the substantia nigra and ventral tegmental area in a transgenic rat model of HD (tgHD). Since there were no changes in the total number of cells in those regions, we hypothesized that changes in cell phenotype were taking place. Here, we tested this hypothesis by studying the dorsal raphe nucleus (DRN), which houses dopaminergic and non-dopaminergic (mainly serotonergic) neurons in tgHD rat tissue and postmortem HD human tissue. We found an increased number of dopamine and reduced number of serotonin-containing cells in the DRN of tgHD rats. Similar findings in postmortem HD brain tissue indicate that these changes also occur in patients. Further investigations in the tgHD animal tissue revealed the presence of dopaminergic cell bodies in the B6 raphe region, while in control animals exclusively serotonin-containing cells were found. These data suggest the existence of phenotype changes in monoaminergic neurons in the DRN in HD and shed new light on the neurobiology of clinical neurological symptoms such as chorea and mood changes.
亨廷顿病（HD）的主要运动症状是舞蹈病。舞蹈病的病理解剖学基础尚不清楚，但尸检和临床研究提示与多巴胺能系统有关。我们之前的工作表明，在亨廷顿病的转基因大鼠模型（tgHD）中，黑质和腹侧被盖区的多巴胺能细胞数量增加。由于这些区域的细胞总数没有变化，我们假设细胞表型发生了变化。在这里，我们通过研究中缝背核（DRN）来检验这一假设，该核在 tgHD 大鼠组织和死后 HD 人类组织中含有多巴胺能和非多巴胺能（主要是 5-羟色胺能）神经元。我们发现 tgHD 大鼠的 DRN 中多巴胺能细胞数量增加，5-羟色胺能细胞数量减少。在死后 HD 脑组织中也有类似的发现，表明这些变化也发生在患者中。对 tgHD 动物组织的进一步研究表明，B6 中缝核区域存在多巴胺能细胞体，而在对照动物中仅发现 5-羟色胺能细胞。这些数据表明，在亨廷顿病的 DRN 中单胺能神经元存在表型变化，为舞蹈病和情绪变化等临床神经系统症状的神经生物学提供了新的线索。
