CHU de Québec Research Center and Department of Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier Boul., Québec City, QC, G1V 4G2, Canada.
Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Roma, Italy.
Behav Brain Res. 2021 Feb 26;400:113039. doi: 10.1016/j.bbr.2020.113039. Epub 2020 Dec 3.
Multiple sclerosis is a neurodegenerative disorder characterized by myelin loss in the brain parenchyma. To mimic the disease, mice are fed a cuprizone-supplemented diet for 5 weeks, which leads to demyelination of white and grey matter regions, with the corpus callosum being the most susceptible to cuprizone intoxication. Although this model is highly exploited, classical behavioural tests showed inconsistent results.
In our study, we aimed to use the automated system Intellicage to phenotype the behaviour of cuprizone-fed mice.
Mice were continuously monitored during the 5 weeks of intoxication in their home cages, with minimal interference from the experimenter. Mice were assessed for spontaneous activity, fine movements, and impulsivity.
Consistently, cuprizone-fed mice showed reduced activity and impulsivity throughout the test period. These behavioral results were confirmed by repeating the battery of behavioral tests in a second cohort of cuprizone-fed mice. Our results suggest that the behavioural phenotyping of cuprizone-fed mice using Intellicage is reproducible and sensitive enough to detect changes normally missed in standard behavioral test batteries.
Using a reproducible and standardized method to assess behavioral changes in mice intoxicated with cuprizone is crucial to better understand the disease as well as the functional outcome of treatments.
多发性硬化症是一种神经退行性疾病,其特征是脑实质中的髓鞘丧失。为了模拟这种疾病,研究人员用含有铜锌超氧化物歧化酶的饮食喂养小鼠 5 周,导致白质和灰质区域脱髓鞘,胼胝体对铜锌超氧化物歧化酶中毒最为敏感。尽管这种模型被广泛应用,但经典的行为测试结果并不一致。
在本研究中,我们旨在使用自动化系统 Intellicage 对铜锌超氧化物歧化酶饮食喂养的小鼠进行行为表型分析。
在小鼠 5 周的中毒期间,将其持续置于其自带的饲养笼中进行监测,实验人员的干预最小化。通过自动分析系统评估小鼠的自发活动、精细运动和冲动性。
一致的是,铜锌超氧化物歧化酶饮食喂养的小鼠在整个测试期间表现出活动减少和冲动性降低。这些行为学结果通过在第二批铜锌超氧化物歧化酶饮食喂养的小鼠中重复进行行为测试得到了验证。我们的结果表明,使用 Intellicage 对铜锌超氧化物歧化酶饮食喂养的小鼠进行行为表型分析是可重复的,并且足够敏感,可以检测到通常在标准行为测试中错过的变化。
使用可重复和标准化的方法来评估铜锌超氧化物歧化酶中毒小鼠的行为变化对于更好地理解疾病以及治疗的功能结果至关重要。