Journal
GLIA
Volume 61, Issue 9, Pages 1418-1428Publisher
WILEY
DOI: 10.1002/glia.22522
Keywords
motor neurons; stem cells; cell autonomous; astrocyte activation
Categories
Funding
- National Institutes of Health [R21HD060899, R01NS40538]
- Advancing a Healthier Wisconsin, Quadracci Memorial Fellowship
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Spinal muscular atrophy (SMA) is a genetic disorder caused by the deletion of the survival motor neuron 1 (SMN1) gene that leads to loss of motor neurons in the spinal cord. Although motor neurons are selectively lost during SMA pathology, selective replacement of SMN in motor neurons does not lead to full rescue in mouse models. Due to the ubiquitous expression of SMN, it is likely that other cell types besides motor neurons are affected by its disruption and therefore may contribute to disease pathology. Here we show that astrocytes in SMA7 mouse spinal cord and from SMA-induced pluripotent stem cells exhibit morphological and cellular changes indicative of activation before overt motor neuron loss. Furthermore, our in vitro studies show mis-regulation of basal calcium and decreased response to adenosine triphosphate stimulation indicating abnormal astrocyte function. Together, for the first time, these data show early disruptions in astrocytes that may contribute to SMA disease pathology.
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