| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
We immunohistochemically investigated the spinal cord of patients with amyotrophic lateral sclerosis (ALS), using EAAT1 and EAAT2 antibodies to examine relationships between EAAT1 and EAAT2 immunoreactivity and degeneration of anterior horn neurons. In controls, spinal cord gray matter was densely immunostained by antibodies, whereas the white matter was generally not immunostained. In ALS patients, EAAT1 immunoreactivity was relatively well-preserved in the gray mater. In contrast, EAAT2 immunoreactivity in anterior horns correlated with the degree of neuronal loss of anterior horn cells : in the patients with mild neuronal depletion, anterior horns were densely immunostained by the antibody, whereas in the patients with severe neuronal loss, EAAT2 expression was markedly reduced. Thus, we demonstrate a difference in EAAT1 and EAAT2 immunoreactivity in different stages of progression in ALS, as a feature of the pathomechanism of this disease. We also performed an immunohistochemical s
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tudy of the spinal cords of transgenic mice with a G93A mutant SOD1 gene, using antibodies to inducible nitric oxide synthase (iNOS) and nitrotyrosine (NT) to characterize the temporal and topographic distribution of the immunoreactivity, thus illuminating the possible role of increased oxidative damage to the motor system in the neurodegenerative process. The control mice showed no positive iNOS or NT immunoreactivity at any age. In contrast, in the transgenic mice, at 24 weeks (early presymptomatic stage), the anterior horn neurons were occasionally immunostained for iNOS and NT ; at 28 weeks (late presymptomatic stage), they were not uncommonly immunostained ; at 32 weeks (early symptomatic stage) and 35 weeks (end-stage), positive iNOS and NT immunoreactivity was frequently observed in proliferated reactive astrocytes as well as in the somata of the anterior horn cells. The selective localization of positive iNOS and NT immunoreactivity in the anterior horn neurons suggests that oxidative stress may be involved in the pathomechanism of degeneration of motor neurons in this transgenic mice. Less
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