Journal
BEHAVIOURAL BRAIN RESEARCH
Volume 250, Issue -, Pages 351-360Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2013.05.025
Keywords
Memory; Aging; SAM; Oxidative stress; Hyperphosphorylated tau; Nobiletin
Categories
Funding
- Ministry of Agriculture, Forestry, and Fisheries of Japan
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Japan Society for the Promotion of Science [22390046, 23659135, 23790290, 24111518]
- Smoking Research Foundation
- Brain Research Center [2012k001115]
- Ministry of Science and Technology, Republic of Korea
- Grants-in-Aid for Scientific Research [24111518, 23659135, 23790290] Funding Source: KAKEN
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Senescence-accelerated mouse prone 8 (SAMP8) is a model of aging characterized by the early onset of learning and memory impairment and various pathological features of Alzheimer's disease (AD). Our recent studies have demonstrated that nobiletin, a polymethoxylated flavone from citrus peels, ameliorates learning and memory impairment in olfactory-bulbectomized mice, amyloid precursor protein transgenic mice, and NMDA receptor antagonist-treated mice. Here, we present evidence that this natural compound improves age-related cognitive impairment and reduces oxidative stress and tau phosphorylation in SAMP8 mice. Treatment with nobiletin (10 or 50 mg/kg) reversed the impairment of recognition memory and context-dependent fear memory in SAMP8 mice. Treatment with nobiletin also restored the decrease in the GSH/GSSG ratio in the brain of SAMP8 mice. In addition, increases in glutathione peroxidase and manganese-superoxide dismutase activities, as well as a decrease in protein carbonyl level, were observed in the brain of nobiletin-treated SAMP8 mice. Furthermore, nobiletin reduced tau phosphorylation in the hippocampus of SAMP8 mice. Together, the markedly beneficial effects of nobiletin represent a potentially useful treatment for ameliorating the learning and memory deficits, oxidative stress, and hyperphosphorylation of tau in aging as well as age-related neurodegenerative diseases such as AD. (C) 2013 Elsevier B.V. All rights reserved.
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