Weighted cart pull: A novel outcome measure for sustained motor function in mice

Area of Science:

• Gerontology
• Neuroscience
• Physiology

Background:

• Sarcopenia, an age-related loss of muscle mass and strength, significantly impacts older adults' independence and quality of life.
• Currently, effective treatments for sarcopenia are lacking, necessitating improved preclinical models for translational research.
• Assessing sustained motor function in aged mouse models is crucial for developing and testing potential interventions.

Purpose of the Study:

• To develop and validate a novel assessment, the weighted cart pull (WCP) test, for measuring sustained motor function in aged mice.
• To evaluate the reliability and phenotypic differences of the WCP test between young and old mice.
• To correlate WCP performance with established measures of neuromuscular and muscle physiology.

Main Methods:

• The weighted cart pull (WCP) test involved mice pulling an incrementally weighted cart up a ramp until failure.
• Reliability was assessed through inter- and intra-rater evaluations in middle-aged mice.
• Young and old mice were tested using WCP, all-limb grip, and rotarod; further correlations involved in vivo electrophysiology and muscle physiology.

Main Results:

• The WCP test demonstrated high intra-rater repeatability (ICC=0.611, P=0.018).
• Significant phenotypic differences in WCP performance were observed between young and old mice (P < 0.0001).
• WCP results strongly correlated with all-limb grip strength, neuromuscular function (nerve stimulation decrement), muscle torque, and muscle mass.

Conclusions:

• The weighted cart pull (WCP) test is a reliable and valid measure of sustained motor function in mice.
• WCP effectively differentiates between young and aged phenotypes, making it valuable for sarcopenia research.
• This cost-effective WCP method enhances preclinical assessments of age-related muscle decline and potential therapeutic interventions.