Stress Hormone Leads to Memory Deficits and Altered Tau Phosphorylation in a Model of Alzheimer's Disease

摘要: Several studies have linked stress with Alzheimer’s disease (AD) vulnerability; however, the mechanism remains to be fully elucidated. In current paper, we investigated role of glucocortitcoids on AD-like phenotype. We administered glucocorticoid dexamethasone Tg2576 mice for 4 weeks and then its effect memory, amyloid-β tau levels, metabolism. At end treatment period, observed that receiving had a significant impairment in fear conditioning paradigm compared controls. Dexamethasone-treated animals showed increase amount brain soluble Aβ40 but no alteration steady state levels precursor protein, AβPP, or major protease enzymes involved metabolism (i.e., ADAM-10, BACE-1, γ-secretase complex). While total protein were unaltered between two groups, found significantly reduced phosphorylation at specific sites mediated by decreases glycogen synthase kinase-3β level activity. Finally, direct correlation memory impairments levels. Our study highlights glucocorticoids play exacerbating cognitive via state.