Analysis of the effects of exercise in a mouse model of Amyotrophic Lateral Sclerosis.

Summary Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of adults characterized by selective loss of fast motor neurons (MN), muscle paralysis and lipid hypermetabolism. Physical exercise could be considered as a therapeutic treatment for ALS. In ALS mice, different running protocols have conflicting effects depending on their intensity. In this scientific context, we compared the neuromuscular adaptations of wild-type and ALS SOD1 G93A mice subjected to treadmill running training and swimming in a current pool that we developed. Under our experimental conditions, swimming preferentially recruits fast motor units and activates large surface MNs, in contrast to running, which preferentially recruits slow motor units (activation of reduced surface MNs and induction of fast-to-slow muscle fiber transitions). Only swimming delays the onset of symptoms and prolongs the life span of ALS mice. It limits MN death in the lumbar spinal cord and maintains skeletal muscle integrity. These effects of swimming are correlated with adaptation of energetic metabolism leading to increased glucose utilization and preservation of lipid stores. Our data highlight a relationship between activation and protection of ALS-sensitive fast motor units. Determining the neuroprotective mechanisms induced by swimming in ALS mice would allow us to propose new therapeutic drug pathways for ALS patients.