Increased cytotoxic potential of microglia from ALS-transgenic mice

Glia. 2004 Nov 1;48(2):179-82. doi: 10.1002/glia.20062.


Amyotrophic lateral sclerosis is a fatal, adult-onset motor neuron disease. A subset of cases is caused by mutations of superoxide dismutase 1 (SOD1) gene. The mechanisms how the mutations in this ubiquitous enzyme mediate the highly selective motor neuron degeneration, however, remain poorly understood. Recent results from transgenic animal models suggest a "non-cell autonomous" mechanism; i.e., cells other than neurons play an active role in motor neuron death. To investigate a possible effect of mtSOD1 on microglial cells, we compared primary cultured microglia from mtSOD1-transgenic mice and nontransgenic litter controls at neonatal (3 days) and adult (60 days) age. We found that mtSOD1 expression increases the production of TNF-alpha and attenuates IL-6-release by LPS-activated adult microglia. Neonatal microglia, however, showed no differences. Our findings suggest an increased cytotoxic potential of adult mtSOD1 microglia, which only becomes apparent after microglial activation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Animals
  • Animals, Newborn
  • Cell Death / genetics
  • Cells, Cultured
  • Disease Models, Animal
  • Gliosis / genetics
  • Gliosis / metabolism
  • Interleukin-6 / metabolism
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Transgenic
  • Microglia / metabolism*
  • Mutation / genetics*
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / genetics


  • Interleukin-6
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1