| First Author | Valente T | Year | 2012 |
| Journal | Neurobiol Aging | Volume | 33 |
| Issue | 9 | Pages | 2186-99 |
| PubMed ID | 22015310 | Mgi Jnum | J:188186 |
| Mgi Id | MGI:5439673 | Doi | 10.1016/j.neurobiolaging.2011.09.019 |
| Citation | Valente T, et al. (2012) C/EBPbeta expression in activated microglia in amyotrophic lateral sclerosis. Neurobiol Aging 33(9):2186-99 |
| abstractText | Neuroinflammation is thought to play a pathogenic role in many neurodegenerative disorders including amyotrophic lateral sclerosis (ALS). In this study we demonstrate that the expression of nitric oxide (NO) synthase-2 (NOS2), and cyclooxygenase (COX)-2 induced by lipopolysaccharide (LPS) with interferon-gamma is higher in microglial-enriched cultures from G93A-SOD1 mice, an ALS animal model, than from wild type mice. The levels of CCAAT/enhancer binding protein beta (C/EBPbeta), a transcription factor that regulates proinflammatory gene expression, are also upregulated in activated G93A-SOD1 microglial cells. In vivo, systemic lipopolysaccharide also induces an exacerbated neuroinflammatory response in G93A-SOD1 mice versus wild type mice, with increased expression of glial fibrillary acidic protein (GFAP), CD11b, nitric oxide synthase-2, cyclooxygenase-2, proinflammatory cytokines, and C/EBPbeta. Finally, we report that C/EBPbeta is expressed by microglia in the spinal cord of ALS patients. This is the first demonstration to our knowledge of microglial C/EBPbeta expression in human disease. Altogether these findings indicate that G93A-SOD1 expression results in an exacerbated pattern of neuroinflammation and suggest that C/EBPbeta is a candidate to regulate the expression of potentially neurotoxic genes in microglial cells in ALS. |
