Evolution of gait abnormalities in SOD1G93A transgenic mice
Evolution of gait abnormalities in SOD1G93A transgenic mice
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DOI：
10.1016/j.brainres.2011.06.033
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发表时间：
2011-08-11
期刊：
影响因子：
2.9
通讯作者：
Navarro, Xavier
中科院分区：
文献类型：
--
作者：
Mancuso, Renzo;Olivan, Sara;Navarro, Xavier
肌萎缩性侧索硬化症是一种神经退行性疾病，其特征在于上、下运动神经元的丧失。临床上，它表现为虚弱、肌肉萎缩和进行性瘫痪，最终导致患者在诊断后2-5年死亡。虽然这些症状在许多情况下导致患者的步态缺陷，但尚未评估模仿该疾病的动物模型的详尽运动特征。在这项工作中，我们评估了运动性能的SOD 1（G93 A）小鼠模型ALS使用计算机跑步机步态分析。SOD 1（G93 A）小鼠出现早期（8周龄）步态异常，表现为后肢站立推进阶段时间增加。这些改变在疾病期间进展，直到完全扰乱正常步态。这一发现对该领域有意义，因为早在8周时就确定了功能终点的显著差异，这可能是解决疗效研究中症状期前小鼠治疗争议的一个步骤。这些结果还指出，跑步机运动的数字化分析可能有助于评估新的治疗方法是否改善了动物的功能结果。(C)2011 Elsevier B. V.保留所有权利。
Amyotrophic lateral sclerosis GALS) is a neurodegenerative disorder characterized by the loss of upper and lower motoneurons. Clinically, it is manifested by weakness, muscle atrophy and progressive paralysis and ends up with patients' death 2-5 years after diagnosis. Although these symptoms lead in many cases to gait deficits in patients, an exhaustive locomotor profile of animal models mimicking the disease has not been assessed yet. In this work we evaluated the locomotor performance of the SOD1(G93A) mouse model of ALS using computerized treadmill gait analysis. SOD1(G93A) mice presented early (8 weeks of age) gait abnormalities, evidenced by an increase in the time of the propulsion phase of hindlimb stance. The alterations progressed during the disease until a complete disturbance of normal gait. This finding is meaningful to the field because the identification of a significant difference in a functional endpoint as early as 8 weeks might be a step forward resolving the debate about treatment of mice prior to the symptomatic phase in efficacy studies. These results also point out that digitizing analysis of treadmill locomotion may be useful to evaluate whether new therapeutic approaches are improving functional outcome of the animals. (C) 2011 Elsevier B.V. All rights reserved.