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


CONCLUSIONS
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.
Alexianu
M E
ME
Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
Kozovska
M
M
Appel
S H
SH
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000818:Animals; D000870:Anterior Horn Cells / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D007074:Immunoglobulin G / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology; D009046:Motor Neurons / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D009410:Nerve Degeneration / Q000235:genetics / Q000276:immunology / Q000473:pathology; D017452:Receptors, IgG / Q000032:analysis; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D013601:T-Lymphocytes / Q000276:immunology
D007074:Immunoglobulin G; D017452:Receptors, IgG; C000606290:SOD1 protein, human; D018799:Intercellular Adhesion Molecule-1; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1