title: Regular exercise prolongs survival in a type 2 spinal muscular atrophy model mouse.
abstract: 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.
authors.affiliation: Université Paris Descartes, Centre Universitaire des Saints-Pères, F-75270 Paris, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Grondard
authors.forename: Olivier
authors.initials: O
authors.lastname: Biondi
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Armand
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lécolle
authors.forename: Bruno
authors.initials: B
authors.lastname: Della Gaspera
authors.forename: Claude
authors.initials: C
authors.lastname: Pariset
authors.forename: Hung
authors.initials: H
authors.lastname: Li
authors.forename: Claude-Louis
authors.initials: CL
authors.lastname: Gallien
authors.forename: Pierre-Paul
authors.initials: PP
authors.lastname: Vidal
authors.forename: Christophe
authors.initials: C
authors.lastname: Chanoine
authors.forename: Frédéric
authors.initials: F
authors.lastname: Charbonnier
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D010805:Physical Conditioning, Animal / Q000379:methods*; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D055532:SMN Complex Proteins; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D015996:Survival Rate; D055540:Survival of Motor Neuron 2 Protein; D013997:Time Factors
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526477:SMN2 protein, human; D055540:Survival of Motor Neuron 2 Protein