title: In Vivo imaging reveals distinct inflammatory activity of CNS microglia versus PNS macrophages in a mouse model for ALS.
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 ∼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.
authors: Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany.
authors: Payam
authors: P
authors: Dibaj
authors: Heinz
authors: H
authors: Steffens
authors: Jana
authors: J
authors: Zschüntzsch
authors: Fabien
authors: F
authors: Nadrigny
authors: Eike D
authors: ED
authors: Schomburg
authors: Frank
authors: F
authors: Kirchhoff
authors: Clemens
authors: C
authors: Neusch
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000201:enzymology / Q000473:pathology*; D000818:Animals; D001369:Axons / Q000473:pathology; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D018450:Disease Progression; D007249:Inflammation / Q000150:complications / Q000473:pathology*; D008264:Macrophages / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000201:enzymology / Q000473:pathology*; D009046:Motor Neurons / Q000473:pathology; D009132:Muscles / Q000294:innervation / Q000473:pathology; D009410:Nerve Degeneration / Q000150:complications / Q000473:pathology; D009469:Neuromuscular Junction / Q000473:pathology; D017933:Peripheral Nervous System / Q000201:enzymology / Q000473:pathology*; D013116:Spinal Cord / Q000201:enzymology / Q000473:pathology*; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1