Influence of Treadmill Exercise on Functional Outcomes in a Mouse Model of Spinal and Bulbar Muscular Atrophy

Background and/or Objectives: Spinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disease characterized by progressive weakness due to motor neuron degeneration. Although exercise is recommended in other neuromuscular conditions, its effect on SBMA remains poorly defined. This study investigates the effect of treadmill exercise on physical function in BAC fxAR121 mice, a preclinical SBMA model.

Design: Preclinical experimental study.

Setting : Laboratory at an academic institution.

Participants : 26-week BAC fxAR121 mice and age-matched wildtypes.

Interventions: Mice were randomly assigned to a stationary group or treadmill running on either a horizontal or 15° downhill gradient. Exercising mice followed the same schedule for six weeks. Body weight, four-limb grip strength, and runtime were recorded weekly.

Main Outcome Measures: Longitudinal changes in grip strength, endurance, and weight, with comparisons between groups.

Results: All mice showed a significant decrease in runtime from the first to the last week (p = 0.022). Exercising SBMA mice showed a 15% decline in grip strength (p = 0.036) and 5% decline in weight (p = 0.013). SBMA stationary and exercise mice didn’t differ in the rate of decline in grip strength (p = 0.9767) or weight (p = 0.842). Wildtypes showed a significant improvement in grip strength (p = 0.0261), gaining strength faster than both SBMA groups. No differences were observed between horizontal and vertical gradients in runtime (p = 0.111), grip strength (p = 0.115), or weight (p = 0.163) in SBMA or wildtypes.

Conclusions: SBMA mice exhibited declines in grip strength and weight regardless of exercise, suggesting that treadmill exercise neither exacerbates nor improves SBMA progression. Wildtypes showed improvement in grip strength after exercise, highlighting the differential effects between healthy and diseased animals. This shows the need for further research to explore alternative therapies for SBMA. Although exercise didn't affect disease progression, we’re now investigating molecular changes in our mice to identify appropriate interventions for SBMA patients.