Novel test of motor and other dysfunctions in mouse neurological disease models.

Novel test of motor and other dysfunctions in mouse neurological disease models.
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DOI:
10.1016/j.jneumeth.2013.10.004
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发表时间:
2014-01-15
影响因子:
3
通讯作者:
Mody, Istvan
Mody, Istvan
中科院分区:
医学4区
文献类型:
--
作者:
Barth, Albert M. I.;Mody, Istvan

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正如人类神经系统疾病一样,相应的小鼠模型也存在多种缺陷。在这类模型中评估疾病进展或潜在治疗效果需要使用耗时的多种测试,通常还需要大量稀缺的转基因动物。 在此,我们介绍一种新颖且简单的单摄像头装置和分析软件,用于对在钢丝网上行走的小鼠进行详细的运动功能评估,该装置可提供复杂的三维信息(瞬时位置、速度、行进距离、足部失误深度、持续时间、位置、与运动速度的关系等)。 我们研究了3组具有不同神经功能缺陷的小鼠:1)单侧运动皮质卒中;2)中等剂量乙醇的影响;3)衰老(96 - 99周龄)。我们发现,卒中后的恢复可根据运动功能缺陷的显著不同特征分为不同阶段,有些类似于人类的运动忽视综合征。接受中等剂量酒精处理的小鼠和老年小鼠表现出特定的运动和探索缺陷。 其他测试部分或完全依赖手动视频分析,这在分析中引入了显著的主观因素,并且只分析运动功能的一个方面。 我们这种新颖的实验方法提供了有关运动障碍以及运动/探索活动的全新的复杂信息。它对于详细描述小鼠中广泛的人类神经系统疾病模型,以及更准确地评估疾病进展或治疗效果应该是有用的。
Just like human neurological disorders, corresponding mouse models present multiple deficiencies. Estimating disease progression or potential treatment effectiveness in such models necessitates the use of time consuming and multiple tests usually requiring a large number of scarcely available genetically modified animals. Here we present a novel and simple single camera arrangement and analysis software for detailed motor function evaluation in mice walking on a wire mesh that provides complex 3D information (instantaneous position, speed, distance traveled, foot fault depth, duration, location, relationship to speed of movement, etc.). We investigated 3 groups of mice with various neurological deficits: 1) unilateral motor cortical stroke; 2) effects of moderate ethanol doses; and 3) aging (96–99 weeks old). We show that post stroke recovery can be divided into separate stages based on strikingly different characteristics of motor function deficits, some resembling the human motor neglect syndrome. Mice treated with moderate dose of alcohol and aged mice showed specific motor and exploratory deficits. Other tests rely either partially or entirely on manual video analysis introducing a significant subjective component into the analysis, and analyze a single aspect of motor function. Our novel experimental approach provides qualitatively new, complex information about motor impairments and locomotor/exploratory activity. It should be useful for the detailed characterization of a broad range of human neurological disease models in mice, and for the more accurate assessment of disease progression or treatment effectiveness.
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