Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative adult-onset disease characterized by a selective loss of fast motoneurons (MN), muscle paralysis and lipidic hyper-metabolism. Physical exercise could be used as therapy in ALS. However, the use of different running-based training protocols in ALS mice led to contradictory results, suggesting that exercise effects might depend on exercise intensity. In this scientific context, we have recently designed a new swimming-based training protocol associated with high frequency and amplitude limb movements. We analyzed the neuromuscular adaptations induced by a swimming or a running programs, in wild-type and SOD1G93A ALS mice. In our experimental conditions, swimming predominantly requests rapid motor units and activates larger-sized MN, contrary to treadmill running which predominantly requests slow motor units (mediumsized MN activation and fast-to-slow transitions in muscle fiber). In ALS mice, swimming unlike running results in a significant delay in the onset of symptoms and in a survival improvement by about 25 days. It limits the death of MN and the astrogliosis in the lumbar spinal cord, and maintains the skeletal muscle integrity. These effects are correlated with the swimming-induced adaptation of energetic metabolism leading to an increase in the glucose uptake and the maintenance of the lipid reserves in ALS mice. All these data highlight a strong relationship between activation and protection of the fast motor units preferentially affected in ALS. The determination of neuroprotection mechanisms induced by swimming in ALS mice would allow new molecular therapeutic strategies for ALS patients
