In Vivo Imaging Reveals Distinct Inflammatory Activity of CNS Microglia versus PNS Macrophages in a Mouse Model for ALS
2011 | journal article. A publication with affiliation to the University of Göttingen.
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In Vivo Imaging Reveals Distinct Inflammatory Activity of CNS Microglia versus PNS Macrophages in a Mouse Model for ALS
Dibaj, P.; Steffens, H.; Zschuentzsch, J.; Nadrigny, F.; Schomburg, E. D.; Kirchhoff, F. & Neusch, C. (2011)
PLoS ONE, 6(3) art. e17910. DOI: https://doi.org/10.1371/journal.pone.0017910
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Details
- Authors
- Dibaj, Payam; Steffens, Heinz; Zschuentzsch, Jana; Nadrigny, Fabien; Schomburg, Eike D.; Kirchhoff, Frank; Neusch, Clemens
- Abstract
- Mutations in the enzyme superoxide dismutase-1 (SOD1) cause hereditary variants of the fatal motor neuronal disease Amyotrophic lateral sclerosis (ALS). Pathophysiology of the disease is non-cell-autonomous: neurotoxicity is derived not only from mutant motor neurons but also from mutant neighbouring non-neuronal cells. In vivo imaging by two-photon laser-scanning microscopy was used to compare the role of microglia/macrophage-related neuroinflammation in the CNS and PNS using ALS-linked transgenic SOD1(G93A) mice. These mice contained labeled projection neurons and labeled microglia/macrophages. In the affected lateral spinal cord (in contrast to non-affected dorsal columns), different phases of microglia-mediated inflammation were observed: highly reactive microglial cells in preclinical stages (in 60-day-old mice the reaction to axonal transection was similar to 180% of control) and morphologically transformed microglia that have lost their function of tissue surveillance and injury-directed response in clinical stages (reaction to axonal transection was lower than 50% of control). Furthermore, unlike CNS microglia, macrophages of the PNS lack any substantial morphological reaction while preclinical degeneration of peripheral motor axons and neuromuscular junctions was observed. We present in vivo evidence for a different inflammatory activity of microglia and macrophages: an aberrant neuroinflammatory response of microglia in the CNS and an apparently mainly neurodegenerative process in the PNS.
- Issue Date
- 2011
- Status
- published
- Publisher
- Public Library Science
- Journal
- PLoS ONE
- ISSN
- 1932-6203