Objective: To determine the suitability of a motorized wheel as a forced exercise modality that does not rely on aversive stimuli for use in Parkinson’s model mice.

Background: Physical activity is associated with more slowly progressing symptoms in Parkinson’s Disease (PD) patients. This has prompted research seeking to elucidate the underlying mechanism. However, modeling exercise in animals is a challenge both technically and in interpretation. There are several models of exercise used in mice, with the simplest involving access to a wheel for voluntary exercise. However, this is difficult to experimentally control and dose. Alternatively, forced exercise models address this concern but commonly rely on aversive stimuli, which may induce stress that attenuates therapeutic benefit. 
The use of a motorized exercise wheel is an alternative approach to forced exercise that has been used in cancer models and may hold promise for use in mouse models of PD. However, preliminary tests suggest that compliance with this “forced” exercise is poor, even in wildtype mice. A pilot study was thus conducted to determine how reliably mice could be trained to run at the speeds typically used in exercise interventions for PD.

Method: In this study, we examined the quality of exercise in 10 C57Bl/6J mice subjected to forced wheel exercise. We used commercially available forced running wheels and a published training protocol that gradually trains mice to run at up to 12m/s over 5 weeks. Quality of exercise was graded by analyzing video recordings of the last 3 exercise sessions, with an animal considered to be exercising at any given timepoint only if it was actively running rather than grabbing onto the wheel or sliding. Particular attention was paid to how many mice would reliably run at 12m/min, with an a priori goal of more than 90% of the mice running for more than 90% of the 12m/min interval.

Results: Of the 10 mice running this protocol, 3 exercised at 12m/min more than 90% of the time. In addition, 4 mice ran at that speed less than 10% of the time. A third group of 3 mice were less consistent. Mice who did not run either grabbed onto the wheel and rode it around.

Conclusion: The exercise performance of the mice showed that most ran very inconsistently at 12m/min. Although the motorized exercise wheel allows for controllable exercise without aversive stimuli, it will require modification in order to achieve reliable results.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/challenges-in-implementing-relevant-exercise-interventions-in-mouse-models-of-parkinsons-disease/