1 Department of Integrated Biological Platform Sciences, GlaxoSmithKline, R&D China, Shanghai, China.
2 Neurodegeneration DPU, GlaxoSmithKline, R&D China, Shanghai, China.
ASN Neuro. 2017 Jul-Aug;9(4):1759091417725174. doi: 10.1177/1759091417725174.
The cuprizone model is a well-established and investigated paradigm to study demyelination and remyelination in rodents. Cuprizone is usually administrated by mixing in the powdered or pelleted rodent chow. However, since cuprizone is sensitive to the environment and the consumption of it varies between different animals, the major issue is the discrepancy in demyelination of the animals. This study reports the development of the cuprizone model by gavage administrations in mice. Following testing a series of doses of cuprizone, 400 mg/kg/day was found to be the best dosage to induce dramatic and consistent demyelination after 5 weeks of administration; while remyelination quickly occurred after 9 days of cuprizone withdrawal. The advantage of this alternative model is that the consumption of cuprizone could be well controlled, and the mice were exposed to the same dose of cuprizone. Thus, the variation in demyelination was minimized. This alternative cuprizone dosing regime minimizes the interanimal variability on demyelination and hence provides a consistent model for pharmacological evaluations, in addition to reducing the number of animals used in the experiments.
铜灰模型是一种成熟且经过充分研究的啮齿动物脱髓鞘和髓鞘再生模型。通常通过将铜灰混入粉末状或颗粒状啮齿动物饲料中进行给药。然而，由于铜灰对环境敏感，且不同动物的摄入量不同，因此主要问题是动物脱髓鞘的差异。本研究报告了通过灌胃给予小鼠铜灰建立模型的方法。在测试了一系列铜灰剂量后，发现每天 400mg/kg 的剂量在给药 5 周后可诱导明显且一致的脱髓鞘；而在停止铜灰摄入 9 天后，髓鞘迅速再生。这种替代模型的优点是可以很好地控制铜灰的摄入量，并且所有小鼠都暴露于相同剂量的铜灰。因此，脱髓鞘的变异性最小化。这种替代的铜灰给药方案最大限度地减少了脱髓鞘过程中的动物间变异性，从而为药理学评估提供了一个一致的模型，同时减少了实验中使用的动物数量。
