Possible pathogenic role of muscle cell dysfunction in motor neuron death in spinal muscular atrophy

S Guettier‐Sigrist, B Hugel, G Coupin… - Muscle & Nerve …, 2002 - Wiley Online Library
S Guettier‐Sigrist, B Hugel, G Coupin, JM Freyssinet, P Poindron, JM Warter
Muscle & Nerve: Official Journal of the American Association of …, 2002Wiley Online Library
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 …
Abstract
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. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000–000, 2002
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