Amende Ivo, Kale Ajit, McCue Scott, Glazier Scott, Morgan James P, Hampton Thomas G
Division of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
J Neuroeng Rehabil. 2005 Jul 25;2:20. doi: 10.1186/1743-0003-2-20.
Gait is impaired in patients with Parkinson's disease (PD) and Huntington's disease (HD), but gait dynamics in mouse models of PD and HD have not been described. Here we quantified temporal and spatial indices of gait dynamics in a mouse model of PD and a mouse model of HD.
Gait indices were obtained in C57BL/6J mice treated with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg/day for 3 days) for PD, the mitochondrial toxin 3-nitropropionic acid (3NP, 75 mg/kg cumulative dose) for HD, or saline. We applied ventral plane videography to generate digital paw prints from which indices of gait and gait variability were determined. Mice walked on a transparent treadmill belt at a speed of 34 cm/s after treatments.
Stride length was significantly shorter in MPTP-treated mice (6.6 +/- 0.1 cm vs. 7.1 +/- 0.1 cm, P < 0.05) and stride frequency was significantly increased (5.4 +/- 0.1 Hz vs. 5.0 +/- 0.1 Hz, P < 0.05) after 3 administrations of MPTP, compared to saline-treated mice. The inability of some mice treated with 3NP to exhibit coordinated gait was due to hind limb failure while forelimb gait dynamics remained intact. Stride-to-stride variability was significantly increased in MPTP-treated and 3NP-treated mice compared to saline-treated mice. To determine if gait disturbances due to MPTP and 3NP, drugs affecting the basal ganglia, were comparable to gait disturbances associated with motor neuron diseases, we also studied gait dynamics in a mouse model of amyotrophic lateral sclerosis (ALS). Gait variability was not increased in the SOD1 G93A transgenic model of ALS compared to wild-type control mice.
The distinct characteristics of gait and gait variability in the MPTP model of Parkinson's disease and the 3NP model of Huntington's disease may reflect impairment of specific neural pathways involved.
帕金森病（PD）和亨廷顿病（HD）患者存在步态障碍，但尚未对PD和HD小鼠模型的步态动力学进行描述。在此，我们对PD小鼠模型和HD小鼠模型的步态动力学时间和空间指标进行了量化。
对C57BL/6J小鼠进行如下处理以获取步态指标：用多巴胺能神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP，30mg/kg/天，共3天）处理建立PD模型，用线粒体毒素3-硝基丙酸（3NP，累积剂量75mg/kg）处理建立HD模型，或用生理盐水处理作为对照。我们应用腹侧平面摄像技术生成数字爪印，从中确定步态指标和步态变异性。处理后，小鼠在透明跑步机带上以34cm/s的速度行走。
与生理盐水处理的小鼠相比，MPTP处理3次后，小鼠的步幅显著缩短（6.6±0.1cm对7.1±0.1cm，P<0.05），步频显著增加（5.4±0.1Hz对5.0±0.1Hz，P<0.05）。一些用3NP处理的小鼠无法表现出协调步态是由于后肢功能障碍，而前肢步态动力学保持完整。与生理盐水处理的小鼠相比，MPTP处理和3NP处理的小鼠步幅间变异性显著增加。为了确定影响基底神经节的药物MPTP和3NP引起的步态障碍是否与运动神经元疾病相关的步态障碍相当，我们还研究了肌萎缩侧索硬化症（ALS）小鼠模型的步态动力学。与野生型对照小鼠相比，ALS的SOD1 G93A转基因模型中的步态变异性没有增加。
帕金森病MPTP模型和亨廷顿病3NP模型中步态及步态变异性的独特特征可能反映了特定神经通路的损伤。
