title: Involvement of brain oxidation in the cognitive impairment in a triple transgenic mouse model of Alzheimer's disease: noninvasive measurement of the brain redox state by magnetic resonance imaging.
abstract: Oxidative stress is considered to be related to the onset and/or progression of Alzheimer's disease (AD), but there is insufficient evidence of its role(s). In this study, we evaluated the relationships between the brain redox state and cognitive function using a triple transgenic mouse model of AD (3 × Tg-AD mouse). One group of 3 × Tg-AD mice started to receive an α-tocopherol-supplemented diet at 2 months of age and another group of 3 × Tg-AD mice was fed a normal diet. The levels of α-tocopherol, reduced glutathione, oxidized glutathione, and lipid peroxidation were decreased in the cerebral cortex and hippocampus at 4 months of age in the 3 × Tg-AD mice fed a normal diet. These reductions were abrogated by the supplementation of α-tocopherol in the diet. During Morris water maze testing, the 3 × Tg-AD mice did not exhibit cognitive impairment at 4 months of age, but started to show cognitive dysfunction at 6 months of age, and α-tocopherol supplementation suppressed this dysfunction. Magnetic resonance imaging (MRI) using 3-hydroxymethyl-proxyl as a probe showed decreases in the signal intensity in the brains of 3 × Tg-AD mice at 4 months of age, and this reduction was clearly attenuated by α-tocopherol supplementation. Taken together, these findings suggest that oxidative stress can be associated with the cognitive impairment in 3 × Tg-AD mice. Furthermore, MRI might be a powerful tool to noninvasively evaluate the increases in reactive radicals, especially those occurring during the early stages of AD.
authors.affiliation: Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima, Japan. ishiyasu@hiroshima-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Ishihara
authors.forename: K
authors.initials: K
authors.lastname: Itoh
authors.forename: Y
authors.initials: Y
authors.lastname: Mitsuda
authors.forename: T
authors.initials: T
authors.lastname: Shimada
authors.forename: T
authors.initials: T
authors.lastname: Kubota
authors.forename: C
authors.initials: C
authors.lastname: Kato
authors.forename: S Y
authors.initials: SY
authors.lastname: Song
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Mori-Yasumoto
authors.forename: S
authors.initials: S
authors.lastname: Sekita
authors.forename: Y
authors.initials: Y
authors.lastname: Kirino
authors.forename: T
authors.initials: T
authors.lastname: Yamazaki
authors.forename: N
authors.initials: N
authors.lastname: Shimamoto
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D015227:Lipid Peroxidation; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D011859:Radiography