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P1‐056: Liver X receptor agonists and altered cellular cholesterol metabolism modulate APP expression in cerebromicrovascular endothelial cells
Author(s) -
Schweinzor Conelea
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.335
Subject(s) - simvastatin , liver x receptor , amyloid precursor protein , cholesterol , medicine , endocrinology , endogeny , biology , secretion , receptor , blood–brain barrier , lipid metabolism , microbiology and biotechnology , chemistry , nuclear receptor , biochemistry , alzheimer's disease , central nervous system , transcription factor , gene , disease
least partially a causative rather thanmerely by-stander role in the neurofibrillary pathology in Alzheimer’s disease (AD). We hypothesized that repeated infectionsduring a lifetime facilitateAD viaoxidative stress and neuroinflammation.Methods: The aim of this study was to evaluate the relationships between acute or repeated peripheral lipopolysaccharide (LPS; 0.5mg/kg; i.p.) administrations, acute and chronic models of infection, and the resulting oxidative injury status in brain of young weaned rats. Reactive oxygen species, nitrites, cholesterol and 4-hydroxynonenal (4-HNE) were used as inflammatory and oxidative stress markers in brain cortex and/or blood. Results: Spatial Learning in Y-maze test demonstrated a differential Learning profile in LPS-treated rats. We have also shown that systemic LPS induced inflammation and oxidative injury as assessed by reactive oxygen species (ROS), NO production and significant decrease in mitochondrial membrane potential associated with a decrease in antioxidant defenses. Our results are consistent with the notion that mitochondrial injury and local oxidative stress may underlie neuronal toxicity as they occur in Alzheimer’s disease. Conclusions: The abnormalities we observed point out oxidative stress as an early event contributing to cell death and cognitive impairments.