Immune reactivity in a mouse model of familial ALS correlates with disease progression

Neurology. 2001 Oct 9;57(7):1282-9. doi: 10.1212/wnl.57.7.1282.


Objective: The cause of motor neuron death in ALS is incompletely understood. This study aims to define the potential involvement of nonneuronal immune-inflammatory factors in the destruction of motor neurons in mutant superoxide dismutase-1 (SOD1) transgenic mice as a model of ALS.

Background: The presence of activated microglia, IgG and its receptor for Fc portion (FcgammaRI), and T lymphocytes in the spinal cord of both patients with ALS and experimental animal models of motor neuron disease strongly suggests that immune-inflammatory factors may be actively involved in the disease process.

Methods: The expression of immune-inflammatory factors was followed in both human mutant (G93A) SOD1 transgenic mice and human wild-type SOD1 transgenic mice, at different ages (40, 80, and 120 days). Fixed, frozen, free-floating sections of the lumbar spinal cord were stained with antibodies against CD11b, IgG, FcgammaRI, intercellular adhesion molecule-1 (ICAM-1), CD3, and glial fibrillary acidic protein.

Results: The earliest change observed was the upregulation of ICAM-1 in the ventral lumbar spinal cord of 40-day-old mutant SOD1 mice. IgG and FcgammaRI reactivities were detected on motor neurons as early as 40 days and on microglial cells at later stages. Microglial activation was first evident in the ventral horn at 80 days, whereas reactive astrocytes and T cells became most prominent in 120-day-old mutant SOD1 mice.

Conclusion: The upregulation of proinflammatory factors during early presymptomatic stages as well as the expansion of immune activation as disease progresses in mutant SOD1 transgenic mice suggest that immune-inflammatory mechanisms could contribute to disease progression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / immunology*
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Anterior Horn Cells / chemistry
  • Anterior Horn Cells / immunology
  • Anterior Horn Cells / pathology
  • Disease Models, Animal
  • Disease Progression
  • Immunoglobulin G / analysis
  • Intercellular Adhesion Molecule-1 / analysis
  • Macrophages / immunology
  • Mice
  • Mice, Transgenic
  • Microglia / immunology
  • Motor Neurons / chemistry
  • Motor Neurons / immunology
  • Motor Neurons / pathology
  • Nerve Degeneration / genetics
  • Nerve Degeneration / immunology
  • Nerve Degeneration / pathology
  • Receptors, IgG / analysis
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase-1
  • T-Lymphocytes / immunology


  • Immunoglobulin G
  • Receptors, IgG
  • SOD1 protein, human
  • Intercellular Adhesion Molecule-1
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1