Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany.
J Mol Neurosci. 2013 Jan;49(1):80-8. doi: 10.1007/s12031-012-9896-0. Epub 2012 Oct 5.
The cuprizone model is a suitable animal model of de- and remyelination secondary to toxin-induced oligodendrogliopathy. From a pharmaceutical point of view, the cuprizone model is a valuable tool to study the potency of compounds which interfere with toxin-induced oligodendrocyte cell death or boost/inhibit remyelinating pathways and processes. The aim of this study was to analyze the vulnerability of neighboring white mater tracts (i.e., the fornix and cingulum) next to the midline of the corpus callosum which is the region of interest of most studies using this model. Male mice were fed cuprizone for various time periods. Different white matter areas were analyzed for myelin (anti-PLP), microglia (anti-IBA1), and astrocyte (anti-GFAP) responses by means of immunohistochemistry. Furthermore, Luxol fast blue-periodic acid Schiff stains were performed to validate loss of myelin-reactive fibers in the different regions. Cuprizone induced profound demyelination of the midline of the corpus callosum and medial parts of the cingulum that was paralleled by a significant astrocyte and microglia response. In contrast, lateral parts of the corpus callosum and the cingulum, as well as the fornix region which is just beneath the midline of the corpus callosum appeared to be resistant to cuprizone exposure. Furthermore, resistant areas displayed reduced astrogliosis and microgliosis. This study clearly demonstrates that neighboring white matter tracts display distinct vulnerability to toxin-induced demyelination. This important finding has direct relevance for evaluation strategies in this frequently used animal model for multiple sclerosis.
铜诱导少突胶质细胞病变导致脱髓鞘和髓鞘再生的模型是一种合适的动物模型。从药物学角度来看，铜模型是一种很有价值的工具，可以研究化合物的效力，这些化合物可以干扰毒素诱导的少突胶质细胞死亡，或促进/抑制髓鞘再生途径和过程。本研究的目的是分析毗邻胼胝体中线的邻近白质束（即穹窿和扣带）的易损性，这是大多数使用该模型的研究的感兴趣区域。雄性小鼠喂食铜一段时间。通过免疫组织化学分析不同的白质区域的髓鞘（抗 PLP）、小胶质细胞（抗 IBA1）和星形胶质细胞（抗 GFAP）反应。此外，还进行了卢索快速蓝-过碘酸希夫染色，以验证不同区域髓鞘反应纤维的丢失。铜诱导胼胝体中线和扣带内侧部分的严重脱髓鞘，伴有明显的星形胶质细胞和小胶质细胞反应。相比之下，胼胝体和扣带的外侧部分以及穹窿区域（刚好在胼胝体中线下方）似乎对铜暴露具有抗性。此外，抗性区域显示出减少的星形胶质细胞增生和小胶质细胞增生。这项研究清楚地表明，相邻的白质束对毒素诱导的脱髓鞘具有明显的易感性。这一重要发现对多发性硬化症中常用的动物模型的评估策略具有直接意义。
