Evaluation of oxidative stress in the brain of a transgenic mouse model of Alzheimer disease by in vivo electron paramagnetic resonance imaging |
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Institution: | 1. Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada;1. Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia;2. Centre for Eye Health, University of New South Wales, Sydney, Australia;3. Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney, Australia |
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Abstract: | Alzheimer disease (AD) is a neurodegenerative disease clinically characterized by progressive cognitive dysfunction. Deposition of amyloid-β (Aβ) peptides is the most important pathophysiological hallmark of AD. Oxidative stress induced by reactive oxygen species is prominent in AD, and several reports suggest the relationship between a change in redox status and AD pathology containing progressive Aβ deposition, the activation of glial cells, and mitochondrial dysfunction. Therefore, we performed immunohistochemical analysis using a transgenic mouse model of AD (APdE9) and evaluated the activity of superoxide dismutase in brain tissue homogenates of APdE9 mice in vitro. Together with those analyses, in vivo changes in redox status with age in both wild-type (WT) and APdE9 mouse brains were measured noninvasively by three-dimensional electron paramagnetic resonance (EPR) imaging using nitroxide (3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-yloxy) as a redox-sensitive probe. Both methods found similar changes in redox status with age, and in particular a significant change in redox status in the hippocampus was observed noninvasively by EPR imaging between APdE9 mice and age-matched WT mice from 9 to 18 months of age. EPR imaging clearly visualized the accelerated change in redox status of APdE9 mouse brain compared with WT. The evaluation of the redox status in the brain of AD model rodents by EPR imaging should be useful for diagnostic study of AD. |
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Keywords: | Alzheimer disease Hippocampus EPR Imaging ROS Redox status Oxidative stress Microglia Astrocytes Amyloid-β Free radicals |
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