Department of Histology and Embryology, Charles University in Prague, Faculty of Medicine in Hradec Králové, Šimkova 870, Hradec Králové, Czech Republic.
Acta Histochem. 2011 Dec;113(8):783-92. doi: 10.1016/j.acthis.2010.11.007. Epub 2010 Dec 28.
Although Huntington's disease (HD) occurs only in humans, the use of animal models is crucial for HD research. New genetic models may provide novel insights into HD pathogenesis, but their relevance to human HD is problematic, particularly owing to a lower number of typically degenerated and dying striatal neurons and consequent insignificant reactive gliosis. Hence, neurotoxin-induced animal models are widely used for histopathological studies. Unlike in humans, the neurodegenerative process (NDP) of the HD phenotype develops very fast after the application of quinolinic acid (QA). For that reason, we compared three groups of rats in more advanced stages (1-12 months) of the QA lesion with 3 representative HD cases of varying length and grade. The outcomes of our long-term histological study indicate that significant parallels may be drawn between HD autopsies and QA-lesioned rat brains (particularly between post-lesional months 3 and 9) in relation to (1) the progression of morphological changes related to the neuronal degeneration, primarily the rarefaction of neuropil affecting the density as well as the character of synapses, resulting in severe striatal atrophy and (2) the participation of oligodendrocytes in reparative gliosis. Conversely, the development and character of reactive astrogliosis is principally conditioned by the severity of striatal NDP in the context of neuron-glia relationship. Despite the above-described differences, morphological patterns in which the components of striatal parenchyma react to the progression of NDP are similar in both human and rat brains. Our study specifies the possibilities of interpreting the morphological findings gained from the QA-induced animal model of HD in relation to HD post-mortem specimens.
尽管亨廷顿病（HD）仅发生在人类中，但动物模型的使用对于 HD 研究至关重要。新的遗传模型可能为 HD 发病机制提供新的见解，但它们与人类 HD 的相关性存在问题，特别是由于纹状体神经元数量减少和死亡，以及相应的反应性神经胶质增生不明显。因此，神经毒素诱导的动物模型广泛用于组织病理学研究。与人类不同，HD 表型的神经退行性过程（NDP）在应用喹啉酸（QA）后非常快地发展。出于这个原因，我们比较了三组在 QA 损伤后处于更晚期（1-12 个月）的大鼠与 3 个具有不同长度和等级的代表性 HD 病例。我们的长期组织学研究结果表明，HD 尸检和 QA 损伤大鼠大脑之间可能存在显著的相似之处（特别是在损伤后 3 个月和 9 个月之间），涉及到：（1）与神经元退化相关的形态变化的进展，主要是影响密度和突触特征的神经突稀疏，导致纹状体严重萎缩；（2）少突胶质细胞参与修复性神经胶质增生。相反，反应性星形胶质细胞的发展和特征主要取决于神经元-胶质细胞关系中纹状体 NDP 的严重程度。尽管存在上述差异，但在两种大脑中，纹状体实质的组成部分对 NDP 进展的反应的形态模式是相似的。我们的研究确定了从 QA 诱导的 HD 动物模型中获得的形态学发现与 HD 尸检标本相关的解释可能性。
