小脑皮质脱髓鞘在杯状铜模型中的作用。

Cerebellar cortical demyelination in the murine cuprizone model.

机构信息

Department of Neurology, Hannover Medical School, Hannover, Germany.

出版信息

Brain Pathol. 2010 Mar;20(2):301-12. doi: 10.1111/j.1750-3639.2009.00271.x. Epub 2009 Apr 7.

Abstract

In multiple sclerosis, demyelination occurs beside the white-matter structures and in the cerebral and cerebellar cortex. We have previously shown that, in the cuprizone model, demyelination is present not only in the corpus callosum but also in the cerebral cortex. Here, we have performed a detailed analysis of the dynamics of de- and remyelination in the cerebellar cortex and white matter at nine timepoints in two cerebellar regions. To induce demyelination, C57BL/6 mice were fed with 0.2% cuprizone for 12 weeks followed by a recovery of 8 weeks. Both cortex and white-matter structures were significantly demyelinated after 12 weeks of cuprizone feeding. Remyelination occurred after withdrawal of cuprizone but was less prominent in the more caudal cerebellar region. Microglia infiltration was prominent in all analyzed cerebellar areas, preceding demyelination by approximately 2-4 weeks, and was delayed in the more caudal cerebellar region. Astrogliosis was also seen but did not reach the extent observed in the cerebrum. In summary, cuprizone feeding provides an excellent model for the investigation of de- and remyelination processes in the cerebellar cortex and white matter. Furthermore, demyelination, microglia and astrocyte changes were different in the cerebellum as compared with the cerebrum, indicating region-dependent pathomechanisms.

摘要

在多发性硬化症中,脱髓鞘发生在白质结构旁边以及大脑和小脑皮层中。我们之前已经表明,在杯状朊病毒模型中,脱髓鞘不仅存在于胼胝体中,也存在于大脑皮层中。在这里,我们在两个小脑区域的九个时间点上对小脑皮层和白质中的脱髓鞘和再髓鞘过程进行了详细分析。为了诱导脱髓鞘,用 0.2%杯状朊病毒喂养 C57BL/6 小鼠 12 周,然后恢复 8 周。在杯状朊病毒喂养 12 周后,皮层和白质结构均明显脱髓鞘。撤去杯状朊病毒后发生再髓鞘化,但在更靠后的小脑区域不太明显。小胶质细胞浸润在所有分析的小脑区域中均很明显,比脱髓鞘早约 2-4 周,在更靠后的小脑区域中延迟。也观察到星形胶质细胞增生,但程度不及大脑。总之,杯状朊病毒喂养为研究小脑皮层和白质中的脱髓鞘和再髓鞘过程提供了极好的模型。此外,与大脑相比,小脑中的脱髓鞘、小胶质细胞和星形胶质细胞变化不同,表明存在依赖于区域的发病机制。

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