Immune reactivity in a mouse model of familial ALS correlates with diseaseprogression

Objective: The cause of motor neuron death in ALS is incompletely understoo d. This study aims to define the potential involvement of nonneuronal immun e-inflammatory factors in the destruction of motor neurons in mutant supero xide dismutase-1 (SOD1) transgenic mice as a model of ALS. Background: The presence of activated microglia, IgG and its receptor for Fe portion (Fc ga mma RI), 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 bo th human mutant (G93A) SOD1 transgenic mice and human wild-type SOD1 transg enic mice, at different ages (40, 80, and 120 days). Fixed, frozen, free-fl oating sections of the lumbar spinal cord were stained with antibodies agai nst CD11b, IgG, Fc gamma RI, intercellular adhesion molecule-1 (ICAM-1), CD 3, and glial fibrillary acidic protein. Results: The earliest change observ ed was the upregulation of ICAM-1 in the ventral lumbar spinal cord of 40-d ay-old mutant SOD1 mice. IgG and Fc gamma RI 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, whe reas reactive astrocytes and T cells became most prominent in 120-day-old m utant SOD1 mice. Conclusion: The upregulation of proinflammatory factors du ring early presymptomatic stages as well as the expansion of immune activat ion as disease progresses in mutant SOD1 transgenic mice suggest that immun e-inflammatory mechanisms could contribute to disease progression.