title: Long-term exercise-specific neuroprotection in spinal muscular atrophy-like mice.
abstract: CONCLUSIONS
  The real impact of physical exercise parameters, i.e. intensity, type of contraction and solicited energetic metabolism, on neuroprotection in the specific context of neurodegeneration remains poorly explored. In this study behavioural, biochemical and cellular analyses were conducted to compare the effects of two different long-term exercise protocols, high intensity swimming and low intensity running, on motor units of a type 3 spinal muscular atrophy (SMA)-like mouse model. Our data revealed a preferential SMA-induced death of intermediate and fast motor neurons which was limited by the swimming protocol only, suggesting a close relationship between neuron-specific protection and their activation levels by specific exercise. The exercise-induced neuroprotection was independent of SMN protein expression and associated with specific metabolic and behavioural adaptations with notably a swimming-induced reduction of muscle fatigability. Our results provide new insight into the motor units' adaptations to different physical exercise parameters and will contribute to the design of new active physiotherapy protocols for patient care.
  Spinal muscular atrophy (SMA) is a group of autosomal recessive neurodegenerative diseases differing in their clinical outcome, characterized by the specific loss of spinal motor neurons, caused by insufficient level of expression of the protein survival of motor neuron (SMN). No cure is at present available for SMA. While physical exercise might represent a promising approach for alleviating SMA symptoms, the lack of data dealing with the effects of different exercise types on diseased motor units still precludes the use of active physiotherapy in SMA patients. In the present study, we have evaluated the efficiency of two long-term physical exercise paradigms, based on either high intensity swimming or low intensity running, in alleviating SMA symptoms in a mild type 3 SMA-like mouse model. We found that 10 months' physical training induced significant benefits in terms of resistance to muscle damage, energetic metabolism, muscle fatigue and motor behaviour. Both exercise types significantly enhanced motor neuron survival, independently of SMN expression, leading to the maintenance of neuromuscular junctions and skeletal muscle phenotypes, particularly in the soleus, plantaris and tibialis of trained mice. Most importantly, both exercises significantly improved neuromuscular excitability properties. Further, all these training-induced benefits were quantitatively and qualitatively related to the specific characteristics of each exercise, suggesting that the related neuroprotection is strongly dependent on the specific activation of some motor neuron subpopulations. Taken together, the present data show significant long-term exercise benefits in type 3 SMA-like mice providing important clues for designing rehabilitation programmes in patients.
authors.affiliation: Université Paris Descartes and INSERM UMRS 1124, 45 rue des Saints-Pères, F-75270, Paris Cedex 06, France.
authors.forename: Farah
authors.initials: F
authors.lastname: Chali
authors.affiliation: Université Paris Descartes and INSERM UMRS 1124, 45 rue des Saints-Pères, F-75270, Paris Cedex 06, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Desseille
authors.affiliation: Université Paris Descartes and INSERM UMRS 1124, 45 rue des Saints-Pères, F-75270, Paris Cedex 06, France.
authors.forename: Léo
authors.initials: L
authors.lastname: Houdebine
authors.affiliation: Institut des Neurosciences Paris-Saclay UMR 9197, CNRS, Bât 32-33, and Service d'Ingénierie Moléculaire des Protéines (DSV/iBiTec-S/SIMOPRO), CEA de Saclay, Bât. 152, 91190, Gif-sur-Yvette, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Benoit
authors.affiliation: BIOMEOSTASIS, Nutritional behavior and metabolic disorders, FST St Jérôme, Service B52, Avenue Escadrille Normandie-Niemen, 13397, Marseille, France.
authors.forename: Thaïs
authors.initials: T
authors.lastname: Rouquet
authors.affiliation: BIOMEOSTASIS, Nutritional behavior and metabolic disorders, FST St Jérôme, Service B52, Avenue Escadrille Normandie-Niemen, 13397, Marseille, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Bariohay
authors.affiliation: Université Paris Descartes and INSERM UMRS 1124, 45 rue des Saints-Pères, F-75270, Paris Cedex 06, France.|Université d'Evry-val-d'Essonne, Bd F. Mitterrand, 91000, Evry, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lopes
authors.affiliation: Université Paris Descartes and INSERM UMRS 1124, 45 rue des Saints-Pères, F-75270, Paris Cedex 06, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Branchu
authors.affiliation: Université Paris Descartes and INSERM UMRS 1124, 45 rue des Saints-Pères, F-75270, Paris Cedex 06, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Della Gaspera
authors.affiliation: Université Paris Descartes and INSERM UMRS 1124, 45 rue des Saints-Pères, F-75270, Paris Cedex 06, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Pariset
authors.affiliation: Université Paris Descartes and INSERM UMRS 1124, 45 rue des Saints-Pères, F-75270, Paris Cedex 06, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Chanoine
authors.affiliation: Université Paris Descartes and INSERM UMRS 1124, 45 rue des Saints-Pères, F-75270, Paris Cedex 06, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Charbonnier
authors.affiliation: Université Paris Descartes and INSERM UMRS 1124, 45 rue des Saints-Pères, F-75270, Paris Cedex 06, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Biondi
mesh_terms: D000818:Animals; D019054:Evoked Potentials, Motor; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009134:Muscular Atrophy, Spinal / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D010805:Physical Conditioning, Animal / Q000379:methods*; D005082:Physical Exertion; D012420:Running; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics / Q000378:metabolism; D013550:Swimming
chemical_list: D055533:Survival of Motor Neuron 1 Protein