Gait dynamics in mouse models of Parkinson's disease and Huntington's disease

被引：118

作者：

Amende I. ^{[1
]}

Kale A. ^{[2
]}

McCue S. ^{[2
]}

Glazier S. ^{[2
]}

Morgan J.P. ^{[1
]}

Hampton T.G. ^{[1
,2
]}

机构：

[1] Division of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston

[2] CuraVita Corporation, Boston

来源：

Journal of NeuroEngineering and Rehabilitation | / 2卷 / 1期

关键词：

Gait variability; Gait; Mouse models; Neurodegeneration; Movement disorders; Amyotrophic Lateral Sclerosis; SOD1;

D O I：

10.1186/1743-0003-2-20

中图分类号：

学科分类号：

摘要：

Background: 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. Methods: 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. Results: 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. Conclusion: 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. © 2005 Amende et al; licensee BioMed Central Ltd.

引用

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