Possible pathogenic role of muscle cell dysfunction in motor neuron death in spinal muscular atrophy.
We have previously shown that myofibers formed by fusion of muscle satellite cells from spinal muscular atrophy (SMA) I or II undergo degeneration 1 to 3 weeks after innervation by rat embryonic spinal cord explants, whereas normal myofibers survive for several months. In the "muscle component" of the coculture, the only cells responsible for the degeneration are the SMA muscle satellite cells. Moreover, SMA muscle satellite cells do not fuse as rapidly as do normal muscle satellite cells. To determine whether death of muscle cells precedes that of motor neurons, we studied the origin and kinetics of release of apoptotic microparticles. In SMA cocultures, motor neuron apoptosis occurred before myofiber degeneration becomes visible, indicating that SMA myofibers were unable to sustain survival of motor neurons. In normal cocultures, motor neuron apoptosis occurred 4 days after innervation. However, it did not continue beyond 2 days. These results strengthen the hypothesis that SMA is due to a defect in neurotrophic muscle cell function.
Guettier-Sigrist
Séverine
S
Université Louis Pasteur, Faculté de Pharmacie, Laboratoire de Pathologie des Communications entre Cellules Nerveuses et Musculaires, Unité Propre de Recherche de l'Enseignement Supérieur, Illkirch, France.
Hugel
Bénédicte
B
Faculté de Médecine, Institut d'Hématologie, 67000 Strasbourg, France.
Coupin
Gilliane
G
Université Louis Pasteur, Faculté de Pharmacie, Laboratoire de Pathologie des Communications entre Cellules Nerveuses et Musculaires, Unité Propre de Recherche de l'Enseignement Supérieur, Illkirch, France.
Freyssinet
Jean-Marie
JM
Faculté de Médecine, Institut d'Hématologie, 67000 Strasbourg, France.
Poindron
Philippe
P
Université Louis Pasteur, Faculté de Pharmacie, Laboratoire de Pathologie des Communications entre Cellules Nerveuses et Musculaires, Unité Propre de Recherche de l'Enseignement Supérieur, Illkirch, France.
Warter
Jean-Marie
JM
Université Louis Pasteur, Faculté de Pharmacie, Laboratoire de Pathologie des Communications entre Cellules Nerveuses et Musculaires, Unité Propre de Recherche de l'Enseignement Supérieur, Illkirch, France.|Faculté de Médecine, Service des Maladies du Nerf et du Muscle, 67000 Strasbourg, France.
D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D002467:Cell Nucleus / Q000502:physiology; D018920:Coculture Techniques; D006801:Humans; D007700:Kinetics; D009046:Motor Neurons / Q000502:physiology*; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology*; D009134:Muscular Atrophy, Spinal / Q000473:pathology / Q000503:physiopathology*; D051381:Rats / Q000196:embryology; D012016:Reference Values; D013997:Time Factors