A translational approach to capture gait signatures of neurological disorders in mice and humans.
A translational approach to capture gait signatures of neurological disorders in mice and humans.
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DOI：
10.1038/s41598-017-03336-1
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发表时间：
2017-06-12
影响因子：
4.6
通讯作者：
VanderHorst VG
中科院分区：
文献类型：
--
作者：
Broom L;Ellison BA;Worley A;Wagenaar L;Sörberg E;Ashton C;Bennett DA;Buchman AS;Saper CB;Shih LC;Hausdorff JM;VanderHorst VG
一种在神经学条件下捕捉步态特征的方法，允许将人类步态与动物模型进行比较，将在翻译研究中具有重要价值。然而，步态参数的速度依赖性以及四足动物和两足动物之间的差异使得这种比较具有挑战性。在这里，我们提出了一种方法，它考虑了行走过程中速度的变化，并允许跨物种转换。在老鼠身上，我们将空间和时间步态参数表示为速度的函数，并建立了回归模型，可以重复地捕捉行走过程中这些关系的特征。在实验性帕金森病模型中，代表这些关系的回归曲线偏离了基线，暗示着步态特征的变化，但模型之间存在显著差异。健康人的步态参数遵循类似的严格的速度依赖关系，而帕金森患者的步态参数发生了变化，类似于一些但不是所有的老鼠模型。这种新的方法适合于量化与跨物种中枢神经系统回路功能障碍相关的定性行走异常，识别合适的动物模型，并提供重要的翻译机会。
A method for capturing gait signatures in neurological conditions that allows comparison of human gait with animal models would be of great value in translational research. However, the velocity dependence of gait parameters and differences between quadruped and biped gait have made this comparison challenging. Here we present an approach that accounts for changes in velocity during walking and allows for translation across species. In mice, we represented spatial and temporal gait parameters as a function of velocity and established regression models that reproducibly capture the signatures of these relationships during walking. In experimental parkinsonism models, regression curves representing these relationships shifted from baseline, implicating changes in gait signatures, but with marked differences between models. Gait parameters in healthy human subjects followed similar strict velocity dependent relationships which were altered in Parkinson’s patients in ways that resemble some but not all mouse models. This novel approach is suitable to quantify qualitative walking abnormalities related to CNS circuit dysfunction across species, identify appropriate animal models, and it provides important translational opportunities.