title: Quantitative assessment of gait and neurochemical correlation in a classical murine model of Parkinson's disease.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Research Center for Sectional and Imaging Anatomy, Shandong University School of Medicine, 250012 Jinan, Shandong, China.
authors.forename: Xiao Hong
authors.initials: XH
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Lu
authors.forename: Xiang
authors.initials: X
authors.lastname: Hu
authors.forename: Kam Sze
authors.initials: KS
authors.lastname: Tsang
authors.forename: Wing Hang
authors.initials: WH
authors.lastname: Kwong
authors.forename: Feng Xia
authors.initials: FX
authors.lastname: Wu
authors.forename: Hai Wei
authors.initials: HW
authors.lastname: Meng
authors.forename: Shu
authors.initials: S
authors.lastname: Jiang
authors.forename: Shu Wei
authors.initials: SW
authors.lastname: Liu
authors.forename: Ho Keung
authors.initials: HK
authors.lastname: Ng
authors.forename: Wai Sang
authors.initials: WS
authors.lastname: Poon
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000704:Analysis of Variance; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D020233:Gait Disorders, Neurologic / Q000209:etiology*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D020267:MPTP Poisoning / Q000139:chemically induced / Q000150:complications* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000209:etiology; D011597:Psychomotor Performance / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase