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Live imaging of amyotrophic lateral sclerosis pathogenesis: Disease onset is characterized by marked induction of GFAP in Schwann cells
Author(s) -
Keller A. Florence,
Gravel Mathieu,
Kriz Jasna
Publication year - 2008
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20836
Subject(s) - glial fibrillary acidic protein , amyotrophic lateral sclerosis , spinal cord , biology , pathogenesis , pathology , motor neuron , neuroglia , downregulation and upregulation , schwann cell , astrocyte , neuroscience , immunohistochemistry , central nervous system , anatomy , medicine , immunology , disease , biochemistry , gene
Amyotrophic lateral sclerosis (ALS) is a late‐onset neurological disease characterized by progressive loss of motor neurons. At present, the pathological events precipitating disease onset and the exact pattern of disease progression are not fully understood. Recent studies suggest that glial cells, in particular activated astrocytes, can release factors that can directly kill motor neurons. To further investigate the involvement of glial cells (astrocytes and Schwann cells) in the pathogenesis of ALS, we generated ALS‐(GFAP‐luciferase/SOD G93A ) reporter mouse in which upregulation of glial fibrillary acidic protein (GFAP) can be visualized from live animals throughout the different stages of disease. Our results suggest that the disease in mice is initiated simultaneously in the spinal cord and in the peripheral nerves and is characterized by several cycles of GFAP upregulation. Immunohistochemical analysis confirmed that the induction GFAP bioluminescence signals were associated with the significant increases in GFAP immunoreactivity. The first pathological GFAP signals occurring at 25–30 days were asymptomatic and detectable at the level of lumbar spinal cord projections and at the periphery. These early events were then followed by GFAP promoter inductions that were associated with the distinct clinical symptoms. As expected, the onset of paralysis (112 days) was associated with the gradual and marked GFAP upregulation in the spinal cord. Interestingly, however, the disease onset (90 days) was characterized by sharp and synchronized induction of GFAP in peripheral nerve Schwann cells suggesting that peripheral nerves pathology/denervation and associated Schwann cell stress may play an important role in the ALS pathogenesis. © 2008 Wiley‐Liss, Inc.