Spinal muscular atrophy astrocytes exhibit abnormal calcium regulation and reduced growth factor production. Glia 2013 Sep;61(9):1418-1428
Date
07/11/2013Pubmed ID
23839956Pubmed Central ID
PMC3941074DOI
10.1002/glia.22522Scopus ID
2-s2.0-84880836806 (requires institutional sign-in at Scopus site) 115 CitationsAbstract
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.
Author List
McGivern JV, Patitucci TN, Nord JA, Barabas MA, Stucky CL, Ebert ADAuthors
Allison D. Ebert PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinTeresa Patitucci PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Cheryl L. Stucky PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Adenosine TriphosphateAge Factors
Aldehyde Dehydrogenase
Analysis of Variance
Animals
Animals, Newborn
Astrocytes
Calcium
Cell Line, Transformed
Choline O-Acetyltransferase
Disease Models, Animal
Gene Expression Regulation, Developmental
Glial Cell Line-Derived Neurotrophic Factor
Glial Fibrillary Acidic Protein
Humans
Mice
Mice, Transgenic
Muscular Atrophy, Spinal
Mutation
Nestin
Oxidoreductases Acting on CH-NH Group Donors
Pluripotent Stem Cells
Receptors, Purinergic P2Y2
S100 Proteins
Spinal Cord
Survival of Motor Neuron 1 Protein
Survival of Motor Neuron 2 Protein