Immunocytochemical evidence that amyloid β (1-42) impairs endogenous antioxidant systems in vivo

H. C. Kim, K. Yamada, A. Nitta, A. Olariu, M. H. Tran, M. Mizuno, A. Nakajima, T. Nagai, H. Kamei, W. K. Jhoo, D. H. Im, E. J. Shin, O. P. Hjelle, O. P. Ottersen, S. C. Park, K. Kato, M. E. Mirault, T. Nabeshima

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Amyloid β, the major constituent of the senile plaques in the brains of patients with Alzheimer's disease, is cytotoxic to neurons and has a central role in the pathogenesis of the disease. We have previously demonstrated that potent antioxidants idebenone and α-tocopherol prevent learning and memory impairment in rats which received a continuous intracerebroventricular infusion of amyloid β, suggesting a role for oxidative stress in amyloid β-induced learning and memory impairment. To test the hypothesis, in the present study, we investigated alterations in the immunoreactivity of endogenous antioxidant systems such as mitochondrial Mn-superoxide dismutase, glutathione, glutathione peroxidase and glutathione-S-transferase following the continuous intracerebroventricular infusion of amyloid β for 2 weeks. The infusion of amyloid β (1-42) resulted in a significant reduction of the immunoreactivity of these antioxidant substances in such brain areas as the hippocampus, parietal cortex, piriform cortex, substantia nigra and thalamus although the same treatment with amyloid β (40-1) had little effect. The alterations induced by amyloid β (1-42) were not uniform, but rather specific for each immunoreactive substance in a brain region-dependent manner. These results demonstrate a cytological effect of oxidative stress induced by amyloid β (1-42) infusion. Furthermore, our findings may indicate a heterogeneous susceptibility to the oxidative stress produced by amyloid β.

元の言語English
ページ(範囲)399-419
ページ数21
ジャーナルNeuroscience
119
発行部数2
DOI
出版物ステータスPublished - 27-06-2003
外部発表Yes

    フィンガープリント

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

これを引用

Kim, H. C., Yamada, K., Nitta, A., Olariu, A., Tran, M. H., Mizuno, M., Nakajima, A., Nagai, T., Kamei, H., Jhoo, W. K., Im, D. H., Shin, E. J., Hjelle, O. P., Ottersen, O. P., Park, S. C., Kato, K., Mirault, M. E., & Nabeshima, T. (2003). Immunocytochemical evidence that amyloid β (1-42) impairs endogenous antioxidant systems in vivo. Neuroscience, 119(2), 399-419. https://doi.org/10.1016/S0306-4522(02)00993-4