Sensory neurons do not induce motor neuron loss in a human stem cell model of spinal muscular atrophy

Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circui...

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Bibliographic Details
Published in:PloS one 2014-07, Vol.9 (7), p.e103112-e103112
Main Authors: Schwab, Andrew J, Ebert, Allison D
Format: Article
Language:English
Subjects:
Apoptosis
Atrophy
Axons
Biology and Life Sciences
Calcium
Calcium - analysis
Calcium - metabolism
Cell culture
Cell Line
Cell Survival
Coculture Techniques
Depolarization
Disease
Glutamate
Glutamic acid transporter
Growth factors
Hereditary diseases
Humans
Medicine and Health Sciences
Motor neurons
Motor Neurons - pathology
Muscular Atrophy, Spinal - pathology
Muscular Atrophy, Spinal - physiopathology
Neurobiology
Neurogenesis
Neuromuscular diseases
Neurons
Neurosciences
Paralysis
Pluripotency
Presynapse
Proteins
Rodents
Science
Sensory neurons
Sensory Receptor Cells - pathology
SMN protein
Spinal cord
Spinal muscular atrophy
Stem cell transplantation
Stem cells
Stem Cells - pathology
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Summary:Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0103112