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

Author: Ishihara Y.   Itoh K.   Mitsuda Y.   Shimada T.   Kubota T.   Kato C.   Song S. Y.   Kobayashi Y.   Mori-Yasumoto K.   Sekita S.   Kirino Y.   Yamazaki T.   Shimamoto N.  

Publisher: Informa Healthcare

ISSN: 1071-5762

Source: Free Radical Research, Vol.47, Iss.9, 2013-09, pp. : 731-739

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Abstract

AbstractOxidative 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.

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