Regular Exercise Prolongs Survival in a Type 2 Spinal Muscular Atrophy Model Mouse

• Published in: The Journal of neuroscience 2005-08, Vol.25 (33), p.7615-7622
• Main Authors: Grondard, Clement, Biondi, Olivier, Armand, Anne-Sophie, Lecolle, Sylvie, Gaspera, Bruno Della, Pariset, Claude, Li, Hung, Gallien, Claude-Louis, Vidal, Pierre-Paul, Chanoine, Christophe, Charbonnier, Frederic
• Format: Article
• Language: English
• Subjects: Animals; Cyclic AMP Response Element-Binding Protein - biosynthesis; Cyclic AMP Response Element-Binding Protein - genetics; Development/Plasticity/Repair; Disease Models, Animal; Female; Male; Mice; Mice, Knockout; Mice, Transgenic; Motor Neurons - pathology; Motor Neurons - physiology; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Physical Conditioning, Animal - methods; RNA-Binding Proteins - biosynthesis; RNA-Binding Proteins - genetics; SMN Complex Proteins; Spinal Muscular Atrophies of Childhood - genetics; Spinal Muscular Atrophies of Childhood - mortality; Spinal Muscular Atrophies of Childhood - pathology; Survival of Motor Neuron 2 Protein; Survival Rate; Time Factors
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.1245-05.2005

Several studies indicate that physical exercise is likely to be neuroprotective, even in the case of neuromuscular disease. In the present work, we evaluated the efficiency of running-based training on type 2 spinal muscular atrophy (SMA)-like mice. The model used in this study is an SMN (survival motor neuron)-null mouse carrying one copy of a transgene of human SMN2. The running-induced benefits sustained the motor function and the life span of the type 2 SMA-like mice by 57.3%. We showed that the extent of neuronal death is reduced in the lumbar anterior horn of the spinal cord of running-trained mice in comparison with untrained animals. Notably, exercise enhanced motoneuron survival. We showed that the running-mediated neuroprotection is related to a change of the alternative splicing pattern of exon 7 in the SMN2 gene, leading to increased amounts of exon 7-containing transcripts in the spinal cord of trained mice. In addition, analysis at the level of two muscles from the calf, the slow-twitch soleus and the fast-twitch plantaris, showed an overall conserved muscle phenotype in running-trained animals. These data provide the first evidence for the beneficial effect of exercise in SMA and might lead to important therapeutic developments for human SMA patients.