Department of Pathology, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liege, Liège 4000, Belgium; Prevor Research Laboratories, Valmondois 95760, France.
Prevor Research Laboratories, Valmondois 95760, France.
Exp Neurol. 2024 Sep;379:114851. doi: 10.1016/j.expneurol.2024.114851. Epub 2024 Jun 13.
Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system affecting over 2.5 million people worldwide. Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is a murine model that reproduces the progressive form of MS and serves as a reference model for studying virus-induced demyelination. Certain mouse strains such as SJL are highly susceptible to this virus and serve as a prototype strain for studying TMEV infection. Other strains such as SWR are also susceptible, but their disease course following TMEV infection differs from SJL's. The quantification of motor and behavioral deficits following the induction of TMEV-IDD could help identify the differences between the two strains. Motor deficits have commonly been measured with the rotarod apparatus, but a multicomponent assessment tool has so far been lacking. For that purpose, we present a novel way of quantifying locomotor deficits, gait alterations and behavioral changes in this well-established mouse model of multiple sclerosis by employing automated video analysis technology (The PhenoTyper, Noldus Information Technology). We followed 12 SJL and 12 SWR female mice and their mock-infected counterparts over a period of 9 months following TMEV-IDD induction. We demonstrated that SJL and SWR mice both suffer significant gait alterations and reduced exploration following TMEV infection. However, SJL mice also display an earlier and more severe decline in spontaneous locomotion, especially in velocity, as well as in overall activity. Maintenance behaviors such as eating and grooming are not affected in either of the two strains. The system also showed differences in mock-infected mice from both strains, highlighting an age-related decline in spontaneous locomotion in the SJL strain, as opposed to hyperactivity in the SWR strain. Our study confirms that this automated video tracking system can reliably track the progression of TMEV-IDD for 9 months. We have also shown how this system can be utilized for longitudinal phenotyping in mice by describing useful parameters that quantify locomotion, gait and behavior.
多发性硬化症（MS）是一种影响全球超过 250 万人的中枢神经系统慢性致残性疾病。Theiler 鼠脑炎病毒诱导的脱髓鞘疾病（TMEV-IDD）是一种复制 MS 进行性形式的啮齿动物模型，是研究病毒诱导脱髓鞘的参考模型。某些小鼠品系，如 SJL，对这种病毒高度易感，是研究 TMEV 感染的原型品系。其他品系，如 SWR，也易感，但它们在 TMEV 感染后的疾病过程与 SJL 不同。在诱导 TMEV-IDD 后，对运动和行为缺陷进行定量评估可以帮助确定这两个品系之间的差异。运动缺陷通常用旋转棒装置来测量，但到目前为止，还缺乏多组分评估工具。为此，我们通过使用自动化视频分析技术（The PhenoTyper，Noldus Information Technology），为这个成熟的多发性硬化症小鼠模型提供了一种新的量化运动缺陷、步态改变和行为变化的方法。我们跟踪了 12 只 SJL 和 12 只 SWR 雌性小鼠及其模拟感染对照，在 TMEV-IDD 诱导后 9 个月内进行了观察。我们证明，SJL 和 SWR 小鼠在 TMEV 感染后都有明显的步态改变和探索减少。然而，SJL 小鼠也表现出更早和更严重的自发性运动下降，尤其是在速度和整体活动方面。两种品系的摄食和梳理等维持行为不受影响。该系统还显示了来自两种品系的模拟感染小鼠之间的差异，突出了 SJL 品系中自发性运动随年龄增长的下降，而 SWR 品系则表现为过度活跃。我们的研究证实，这种自动化视频跟踪系统可以在 9 个月内可靠地跟踪 TMEV-IDD 的进展。我们还展示了如何通过描述量化运动、步态和行为的有用参数，将该系统用于小鼠的纵向表型分析。
