Evaluation of oxidative stress in the brain of a transgenic mouse model of Alzheimer disease by in vivo electron paramagnetic resonance imaging.
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.
Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo 060-8543, Japan.
Akihiro
A
Matsumura
Center for Medical Education, Sapporo Medical University, Sapporo 060-8543, Japan.
Miho C
MC
Emoto
Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo 060-8543, Japan.
Syuuichirou
S
Suzuki
Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo 060-8543, Japan.
Naotoshi
N
Iwahara
Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo 060-8543, Japan.
Shin
S
Hisahara
Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo 060-8543, Japan.
Jun
J
Kawamata
Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo 060-8543, Japan.
Hiromi
H
Suzuki
Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo 060-8543, Japan.
Ayano
A
Yamauchi
Department of Systems Innovation, Graduate School of Engineering Science, Osaka University, Osaka 560-8531, Japan.
Hideo
H
Sato-Akaba
Center for Medical Education, Sapporo Medical University, Sapporo 060-8543, Japan.
Hirotada G
HG
Fujii
Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo 060-8543, Japan. Electronic address: shimoha@sapmed.ac.jp.
Shun
S
Shimohama
D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress
Alzheimer disease; Amyloid-β; Astrocytes; EPR; Free radicals; Hippocampus; Imaging; Microglia; Oxidative stress; ROS; Redox status