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Spinal muscular atrophy astrocytes exhibit abnormal calcium regulation and reduced growth factor production
Author(s) -
McGivern Jered V.,
Patitucci Teresa N.,
Nord Joshua A.,
Barabas MarieElizabeth A.,
Stucky Cheryl L.,
Ebert Allison D.
Publication year - 2013
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22522
Subject(s) - sma* , spinal muscular atrophy , smn1 , motor neuron , biology , astrocyte , neuroscience , spinal cord , induced pluripotent stem cell , central nervous system , embryonic stem cell , biochemistry , mathematics , combinatorics , gene
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 SMAΔ7 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.