Department of Neurodegeneration, H. Lundbeck A/S, Ottiliavej 9, 2500 Copenhagen-Valby, Denmark.
Behav Brain Res. 2012 Jan 15;226(2):519-28. doi: 10.1016/j.bbr.2011.10.006. Epub 2011 Oct 12.
Gait disturbances and postural instability represent major sources of morbidity in Parkinson's disease (PD), and respond poorly to current treatment options. Some aspects of gait disturbances can be observed in rodent models of PD; however, knowledge regarding the stability of rodent gait patterns over time is lacking. Here we investigated the temporal constancy and reproducibility of gait patterns in neurologically intact and bilaterally 6-hydroxydopamine (6-OHDA) lesioned rats, by using an automated quantitative gait analysis method (CatWalk). The bilateral neurotoxin injections into the medial forebrain bundle resulted in an average dopamine (DA) loss of 70% in each striata, which corresponds to the DA levels observed in moderate-mid stage human PD. Rats were tested weekly during one month, and we found that in intact rats all parameters investigated remained constant over multiple tests. The 6-OHDA lesioned rats were impaired in several aspects of gait, such as stride length, swing speed, stance duration, step cycle duration, and base of support. However the stance and step cycle deficits were transient, the performance of 6-OHDA lesioned rats were indistinguishable from control rats by the last test session with regard to these parameters. Finally, we found that administration of a single dose of levodopa (L-DOPA) to the 6-OHDA lesioned rats could counteract all but one observed deficits. Based on these findings we conclude that the gait pattern of intact rats is highly reproducible, 6-OHDA lesioned rats display impairments in gait, and L-DOPA can counteract most deficits seen in this model of experimental PD.
步态障碍和姿势不稳是帕金森病（PD）患者主要的致残因素，而目前的治疗选择对此反应不佳。一些与步态障碍相关的特征可以在 PD 的啮齿动物模型中观察到；然而，对于啮齿动物步态模式随时间的稳定性的了解还很缺乏。在这里，我们使用自动化定量步态分析方法（CatWalk），研究了神经完整和双侧 6-羟多巴胺（6-OHDA）损伤大鼠的步态模式的时间稳定性和可重复性。双侧神经毒素注射到中脑导水管周围灰质导致每个纹状体的多巴胺（DA）平均损失 70%，这与中度至中期人类 PD 中观察到的 DA 水平相对应。大鼠在一个月内每周进行测试，我们发现，在完整的大鼠中，所有研究的参数在多次测试中都保持不变。6-OHDA 损伤的大鼠在步态的几个方面存在障碍，例如步幅长度、摆动速度、站立持续时间、步周期持续时间和支撑基础。然而，站立和步周期缺陷是短暂的，在最后一次测试中，6-OHDA 损伤的大鼠在这些参数上与对照组大鼠没有区别。最后，我们发现，给 6-OHDA 损伤的大鼠单次给予左旋多巴（L-DOPA）可以消除除一个观察到的缺陷之外的所有缺陷。基于这些发现，我们得出结论，完整大鼠的步态模式具有高度的可重复性，6-OHDA 损伤的大鼠在步态方面存在障碍，而 L-DOPA 可以抵消该实验性 PD 模型中观察到的大多数缺陷。
