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Open Access Highly Accessed Research article

Quantitative assessment of gait and neurochemical correlation in a classical murine model of Parkinson’s disease

Xiao Hong Wang123, Gang Lu23, Xiang Hu24, Kam Sze Tsang25, Wing Hang Kwong3, Feng Xia Wu12, Hai Wei Meng1, Shu Jiang4, Shu Wei Liu1*, Ho Keung Ng5 and Wai Sang Poon23*

Author Affiliations

1 Research Center for Sectional and Imaging Anatomy, Shandong University School of Medicine, 250012, Jinan, Shandong, China

2 Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China

3 School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China

4 Shenzhen Beike Cell Engineering Research Institute, Shenzhen, China

5 Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China

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BMC Neuroscience 2012, 13:142  doi:10.1186/1471-2202-13-142

Published: 14 November 2012

Abstract

Background

Gait deficits are important clinical symptoms of Parkinson’s disease (PD). However, existing behavioral tests for the detection of motor impairments in rodents with systemic dopamine depletion only measure akinesia and dyskinesia, and data focusing on gait are scarce. We evaluated gait changes in the methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced C57BL/6 murine model of PD by using a computer-assisted CatWalk system. Correlations of gait parameters with tyrosine hydroxylase (TH) protein levels in the substantia nigra (SN) were also investigated.

Results

The gait readouts, including the walking duration, variation of walking speed, step cycle, duty cycle, stance, initial dual stance, terminal dual stance, three- and four-point supports, and the base of support between hind limbs was noted to increase significantly one week after MPTP injection. In contrast, values of the stride length, cadence, swing speed, and diagonal dual support decreased substantially following MPTP treatment (p < 0.05). All of these changes lasted for three weeks after the last MPTP administration. Except for the stance in the fore limbs and the swing speed in the hind limbs, the gait variability in the PD mice showed a closer correlation with the protein levels of TH in the SN than the walking distances in the conventional open field test. Coordination parameters of the regularity index and step pattern were not affected in mice treated with MPTP.

Conclusion

Data of the study suggest that the computer-assisted CatWalk system can provide reliable and objective criteria to stratify gait changes arising from MPTP-induced bilateral lesions in C57/BL6 mice. The extent of gait changes was noted to correlate with the expression of the biomarker for dopaminergic neurons. This novel analytical method may hold promise in the study of disease progression and new drug screening in a murine PD model.

Keywords:
Parkinson’s disease; Gait; MPTP; Tyrosine hydroxylase; Neurochemical correlation