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帕金森病的慢性小鼠模型具有降低的步态模式确定性。

A chronic mouse model of Parkinson's disease has a reduced gait pattern certainty.

作者信息

Kurz Max J, Pothakos Konstantinos, Jamaluddin Sakeena, Scott-Pandorf Melissa, Arellano Chris, Lau Yuen-Sum

机构信息

Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, Houston, TX, United States.

出版信息

Neurosci Lett. 2007 Dec 11;429(1):39-42. doi: 10.1016/j.neulet.2007.09.060. Epub 2007 Oct 5.

Abstract

The purpose of this investigation was to determine if a chronic Parkinson's disease mouse model will display less certainty in its gait pattern due to basal ganglia dysfunction. A chronic Parkinson's disease mouse model was induced by injecting male C57/BL mice with 10 doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25mg/kg) (MPTP) and probenecid (250 mg/kg) (P) over 5 weeks. This chronic model produces a severe and persistent loss of nigrostriatal neurons resulting in dopamine depletion and locomotor impairment. The control mice were treated with probenecid alone. Fifteen weeks after the last MPTP/P treatment, the mice were videotaped in the sagittal plane with a digital camera (60 Hz) as they ran on a motorized treadmill at a speed of 10 m/min. The indices of gait and gait variability were calculated. Stride length was significantly (p=0.016) more variable in the chronic MPTP/P mice. Additionally, the chronic MPTP/P mice had a statistically less certain gait pattern when compared to the control mice (p=0.02). These results suggest that variability in the gait pattern can be used to evaluate changes in neural function. Additionally, our results imply that disorder of the basal ganglia results in less certainty in modulating the descending motor command that controls the gait pattern.

摘要

本研究的目的是确定慢性帕金森病小鼠模型是否会由于基底神经节功能障碍而在步态模式上表现出较低的确定性。通过给雄性C57/BL小鼠在5周内注射10剂1-甲基-4-苯基-1,2,3,6-四氢吡啶(25mg/kg)(MPTP)和丙磺舒(250mg/kg)(P)来诱导慢性帕金森病小鼠模型。这种慢性模型会导致黑质纹状体神经元严重且持续丧失,从而导致多巴胺耗竭和运动障碍。对照小鼠仅用丙磺舒治疗。在最后一次MPTP/P治疗后15周,当小鼠以10m/min的速度在电动跑步机上奔跑时,用数码相机(60Hz)在矢状面拍摄它们。计算步态和步态变异性指标。慢性MPTP/P小鼠的步幅长度变异性显著更高(p = 0.016)。此外,与对照小鼠相比,慢性MPTP/P小鼠的步态模式在统计学上确定性更低(p = 0.02)。这些结果表明,步态模式的变异性可用于评估神经功能的变化。此外,我们的结果表明,基底神经节紊乱导致在调节控制步态模式的下行运动指令方面确定性降低。

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