Regular exercise prolongs survival in a type 2 spinal muscular atrophy model mouse.
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.
Grondard
Clément
C
Université Paris Descartes, Centre Universitaire des Saints-Pères, F-75270 Paris, France.
Biondi
Olivier
O
Armand
Anne-Sophie
AS
Lécolle
Sylvie
S
Della Gaspera
Bruno
B
Pariset
Claude
C
Li
Hung
H
Gallien
Claude-Louis
CL
Vidal
Pierre-Paul
PP
Chanoine
Christophe
C
Charbonnier
Frédéric
F
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
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