Rodent (rats and mice) kinematic gait analysis is a fundamental approach to exhibit genomic and neuro-de/re-generative preclinical research. Recent advancements in technologies and analytic tools now grant a new step towards a fully automatic qualitative and quantitative kinematic gait analysis of observational gait such as foot-tracking systems or marker-based motion capture systems.
In existing footprint tracking systems, the subject is placed on a transparent platform allowing their footprints to be measured from underneath and alterations in gait parameters are then correlated to the observations in human patients. In such conditions, key parameters such as stride length, cadence, step cycle, and limb coordination can be investigated. However, due to a limited anatomical tracked point, one disadvantage of such footprint-based gait analysis is their inability to detect early-phase dysfunction before being caused by the progressive neuronal loss associated with the disease development. Therefore, new systematic approaches had to develop to support a more complete marker-based motion capture. Using the MotoRater system, a state-of-the-art system tracking all anatomical marked points, allows scientists to provide a refine kinematic characterization of mouse models including complementary parameters such as Spatio-temporal inter-limb coordination, body posture, joint angles as well as paw and anatomical point trajectory. The addition of these finetune kinematics features allows an early prediction of motor disease even prior to normally monitored late symptoms.
Researchers at Charles River Discovery Services in Finland University of Eastern Finland, Naason Science Inc., in South Korea and CHDI Management/CHDI Foundation in USA, have conducted experiments in the R6/2 and Q175 mouse models of Huntington’s disease (HD), a well-known inherited neurodegenerative disorder characterized by severe disruption of cognitive and motor functions, including changes in posture and gait.
Using sensitive MotoRater parameters detection and principal component analysis for high-throughput, authors established and determine progressive changes in locomotor patterns across 79 parameters in the R6/2 and Q175 mice. Surprisingly, in R6/2 mice model where HTT gene presents poly-CAG repeats (120 CAG repeats/exon 1/chromosome 4), showed motor disturbances as early as 4 weeks of age. Similar disturbances were identified in homozygous and heterozygous Q175 KI mice at 3 and 6 months of age, respectively. The principal components of the behavioral phenotypes produced two phenotypic scores of progressive postural instabilities based on kinematic parameters and trajectory waveform data, which were shared by both HD models. Interestingly, on R6/2 mice developed forelimb ataxia among these different HD models.
Progressive decreases in movement speed and lower stride distance were observed in R6/2 and Q175 mice like other mouse models of HD. Authors were later-on able to replicate their previous findings of lower stride speed, stride distance, and peak swing speed in 10-week-old R6/2 mice and extended some of them to the younger age of 4 weeks. In foot-tracking systems, a shorter stride distance was also noted in 10-week-old R6/2 mice. In contrast, the automated treadmill video capture system failed to reveal differences in most of these parameters (17-week-old R6/2 mice) possibly due to the forced nature of treadmill test or differential posture adaptation at this advanced stage of the pathology.
Therefore, this study highlights the many advantages of MotoRater marker-based motion capture systems approach which dramatically improves and deepens fine kinematic analysis. This work adds new evidence and early symptoms to the available HD mouse model research toolbox and has the potential to facilitate the development of therapeutics for HD and other debilitating movement disorders with high unmet medical needs.
Heikkinen, T., Bragge, T., Bhattarai, N., Parkkari, T., Jukka Puoliväli, Kontkanen, O.,Sweeney, P., Park, L. C., & Munoz-Sanjuan, I. (2020). Rapid and robust patterns of spontaneous locomotor deficits in mouse models of Huntington’s disease. PLoS ONE. https://doi.org/10.1371/journal.pone.0243052
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