Résumé :
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Amyotrophic Lateral Sclerosis (ALS) is a fatal adult-onset neurodegenerative disease that involves selective loss of motor neurons in the motor cortex, brainstem and spinal cord. The benefits of regular exercise for ALS still remain controversial. The use of different exercise paradigm in mice led to contradictory results, suggesting that exercise effects might depend on exercise protocol. We have recently designed a new swimming-based training protocol associated with high frequency and amplitude exercise. We compared the time course of muscle adaptations to the swimming- and a running-based training exercise in healthy mice. We demonstrated that the magnitude of exercise-induced muscle plasticity proved to be dependent on both the muscle type and the exercise paradigm. Importantly, we showed that, in our experimental conditions, swimming predominantly requests rapid motor units and, consequently, larger-sized lumbar motor-neurons, as indicated by a double labeling using the activity marker c-fos and a ChAT immunodetection. Since ALS is characterized by a preferential loss of fast motor units, involving thus the larger-sized motor neurons, we submitted a population of transgenic hSOD1 mice to our swimming program from 70 days of age, and compared the swimming effects with those of a running protocol. Only the swimming program resulted in a significant delay in the onset of symptoms and in a survival improvement. Furthermore, our results clearly indicated that the swimming-based training imposed on hSOD1 mice protects the motor neurons, contrary to the running-based training. These results strongly suggest that the exercise-activated neurons are selectively protected against cell death, in contrast to resting neurons. In this respect, the molecular mechanism(s) underlying exercise neuroprotection is indicative of an intrinsic modification of the activated neuron. Further identification of these mechanisms may constitute a promising therapeutic way.
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