Intricate interplay between astrocytes and motor neurons in ALS

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 8; pp. E756 - E765
• Main Authors: Phatnani, Hemali P., Guarnieri, Paolo, Friedman, Brad A., Carrasco, Monica A., Muratet, Michael, O’Keeffe, Sean, Nwakeze, Chiamaka, Pauli-Behn, Florencia, Newberry, Kimberly M., Meadows, Sarah K., Tapia, Juan Carlos, Myers, Richard M., Maniatis, Tom
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 19.02.2013; National Acad Sciences
• Series: PNAS Plus
• Subjects: alleles; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - pathology; animal models; Animals; astrocytes; Astrocytes - pathology; Bioinformatics; Biological Sciences; Cell culture; coculture; disease course; Disease Models, Animal; Gene Expression; gene expression regulation; Genes; Humans; Mice; motor neurons; Motor Neurons - pathology; Neurons; PNAS Plus; Proteoglycans - metabolism; Receptors, Transforming Growth Factor beta - metabolism; Rodents; signal transduction; Spinal cord; Spinal Cord - enzymology; Spinal Cord - metabolism; superoxide dismutase; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; transforming growth factor beta; Up-Regulation
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1222361110

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.