Ablation of proliferating microglia does not affect motor neuron degeneration in amyotrophic lateral sclerosis caused by mutant superoxide dismutase

J Neurosci. 2008 Oct 8;28(41):10234-44. doi: 10.1523/JNEUROSCI.3494-08.2008.


Microglial activation is a hallmark of all neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Here, a detailed characterization of the microglial cell population within the spinal cord of a mouse model of familial ALS was performed. Using flow cytometry, we detected three distinct microglial populations within the spinal cord of mice overexpressing mutant superoxide dismutase (SOD1): mature microglial cells (CD11b(+), CD45(low)), myeloid precursor cells (CD11b(+), CD45(int)), and macrophages (CD11b(+), CD45(high)). Characterization of cell proliferation within the CNS of SOD1(G93A) mice revealed that the expansion in microglial cell population is mainly attributable to the proliferation of myeloid precursor cells. To assess the contribution of proliferating microglia in motor neuron degeneration, we generated CD11b-TK(mut-30); SOD1(G93A) doubly transgenic mice that allow the elimination of proliferating microglia on administration of ganciclovir. Surprisingly, a 50% reduction in reactive microglia specifically in the lumbar spinal cord of CD11b-TK(mut-30); SOD1(G93A) doubly transgenic mice had no effect on motor neuron degeneration. This suggests that proliferating microglia-expressing mutant SOD1 are not central contributors of the neurodegenerative process in ALS caused by mutant SOD1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / complications
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / pathology*
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Animals
  • Biomarkers / metabolism
  • CD11b Antigen / metabolism
  • Cell Count
  • Cell Proliferation
  • Cellular Senescence
  • Dendritic Cells / metabolism
  • Disease Progression
  • Mice
  • Mice, Transgenic
  • Microglia / immunology
  • Microglia / pathology*
  • Motor Neurons / pathology*
  • Mutation*
  • Nerve Degeneration / etiology
  • Nerve Degeneration / pathology*
  • Neuroglia / pathology
  • Phenotype
  • Spinal Cord / pathology
  • Stem Cells / pathology
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase-1
  • T-Lymphocytes / pathology


  • Biomarkers
  • CD11b Antigen
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1