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

Abstract

BackgroundGait 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.ResultsThe 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.ConclusionData 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.

Gait analysis in a mouse model resembling Leigh disease

“…Walking speed variation was markedly increased in Ndufs4 −/− mice, indicating hampered and uncoordinated gait. Similar gait abnormalities were found in MPTP-treated C57BL/6 mice, a model for Parkinson's disease [21]. Furthermore, marked differences were found between Ndusf4 −/− and control mice for other dynamic parameters like step cycle, swing speed, body speed and body speed variation.…”

“…Behavioral testing was performed at three different time points (21,35 and 42 days of age). Here we show, similar as described in the literature [27], impaired rotarod performance in Ndufs4 −/− mice, which was significantly different from control mice at 35 and 42 days of age (F2,43 = 35.35, p < .0001) (Fig.…”

“…Major advantage of this paradigm is the objectivity of the system reducing inter-and intra-observer variability. The automated CatWalk gait analysis method is also applied in models involving other types of pain and peripheral nerve damage and movement disorders like Parkinson's disease [21][22][23]. Abnormal gait was described in mice exhibiting (cerebellar) ataxia, by using paw print area, contact area, base of support of the hindpaws, stand, swing and step regularity [24][25][26].…”

Gait analysis in three different 6-hydroxydopamine rat models of Parkinson's disease

“…Test indicators that are limited to monitor either static or dynamic state cannot adequately display both readouts simultaneously [8], and so on. Therefore, although great efforts have been made to measure the gait deficits in these 6-OHDA PD models [5,9,10], the validation and characterization of gait variability is still lacking [11]. In this report we validated gait variability in three different rat PD models of http://dx.doi.org/10.1016/j.neulet.2014.…”

Xenon Improves Neurologic Outcome and Reduces Secondary Injury Following Trauma in an In Vivo Model of Traumatic Brain Injury*

“…Studies using analysis of gait in TBI patients have revealed deficits compared to healthy controls. The CatWalk-XT gait-analysis system has been used to measure deficits in a variety of rodent brain-injury models [65][66][67][68]. Gait analysis one month after injury revealed significant (p<0.05) deficits in the TBI group, in locomotor speed and in the swing speed of all four limbs.…”