title: Intricate interplay between astrocytes and motor neurons in ALS.
abstract: ALS results from the selective and progressive degeneration of motor neurons. Although the underlying disease mechanisms remain unknown, glial cells have been implicated in ALS disease progression. Here, we examine the effects of glial cell/motor neuron interactions on gene expression using the hSOD1(G93A) (the G93A allele of the human superoxide dismutase gene) mouse model of ALS. We detect striking cell autonomous and nonautonomous changes in gene expression in cocultured motor neurons and glia, revealing that the two cell types profoundly affect each other. In addition, we found a remarkable concordance between the cell culture data and expression profiles of whole spinal cords and acutely isolated spinal cord cells during disease progression in the G93A mouse model, providing validation of the cell culture approach. Bioinformatics analyses identified changes in the expression of specific genes and signaling pathways that may contribute to motor neuron degeneration in ALS, among which are TGF-β signaling pathways.
authors: Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032, USA.
authors: Hemali P
authors: HP
authors: Phatnani
authors: Paolo
authors: P
authors: Guarnieri
authors: Brad A
authors: BA
authors: Friedman
authors: Monica A
authors: MA
authors: Carrasco
authors: Michael
authors: M
authors: Muratet
authors: Sean
authors: S
authors: O'Keeffe
authors: Chiamaka
authors: C
authors: Nwakeze
authors: Florencia
authors: F
authors: Pauli-Behn
authors: Kimberly M
authors: KM
authors: Newberry
authors: Sarah K
authors: SK
authors: Meadows
authors: Juan Carlos
authors: JC
authors: Tapia
authors: Richard M
authors: RM
authors: Myers
authors: Tom
authors: T
authors: Maniatis
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D051379:Mice; D009046:Motor Neurons / Q000473:pathology*; D011509:Proteoglycans / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D013116:Spinal Cord / Q000201:enzymology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan; D013482:Superoxide Dismutase
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