Circadian Disruption Reveals a Correlation of an Oxidative GSH/GSSG Redox Shift with Learning and Impaired Memory in an Alzheimer’s Disease Mouse Model

摘要: Abstract It is unclear whether pre-symptomatic Alzheimer's disease (AD) causes circadian disruption or accelerates AD pathogenesis. In order to examine the sensitivity of learning and memory disruption, we altered normal lighting phases by an 8 h shortening dark period every 3 days (jet lag) in APPSwDI NOS2-/- model (AD-Tg) at a young age (4-5 months), when not yet affected compared non-transgenic (non-Tg) mice. Analysis activity 12-12 constant darkness showed only minor differences between AD-Tg non-Tg Jet lag greatly reduced both genotypes during time. Learning on Morris water maze was significantly impaired mice exposed jet lag. However, after training genotypes. caused decrease glutathione (GSH) levels that tended be more pronounced than brains associated increase NADH Lower brain GSH correlated with poor performance maze. These data indicate combination environmental stress together latent mutant amyloid NOS2 knockout contributes cognitive deficits correlate lower levels.