| First Author | de Oliveira J | Year | 2011 |
| Journal | Neuroscience | Volume | 197 |
| Pages | 99-106 | PubMed ID | 21945034 |
| Mgi Jnum | J:184047 | Mgi Id | MGI:5319766 |
| Doi | 10.1016/j.neuroscience.2011.09.009 | Citation | de Oliveira J, et al. (2011) Positive correlation between elevated plasma cholesterol levels and cognitive impairments in LDL receptor knockout mice: relevance of cortico-cerebral mitochondrial dysfunction and oxidative stress. Neuroscience 197:99-106 |
| abstractText | Convergent epidemiological, clinical, and experimental findings indicate that hypercholesterolemia contributes to the onset of Alzheimer's disease (AD)-like dementia, but the exact underlying mechanisms remains unknown. In this study, we evaluated the cognitive performance of mice submitted to a model of hypercholesterolemia, as well as its relationship with mitochondrial dysfunction and oxidative stress, two key events involved in AD pathogenesis. Wild-type C57bl/6 or low density lipoprotein receptor (LDLr)-deficient mice were fed with either standard or cholesterol-enriched diet for a 4-week period and tested for spatial learning and memory in the object location task. LDLr(-)/(-) mice displayed spatial learning and memory impairments regardless of diet. Moreover, LDLr(-)/(-) mice fed cholesterol-enriched diet presented a significant decrease in the mitochondrial complexes I and II activities in the cerebral cortex, which were negatively correlated with respective blood cholesterol levels. Additionally, hypercholesterolemic LDLr(-)/(-) mice presented a significant decrease in glutathione levels, about 40% increase in the thiobarbituric acid-reactive substances levels, as well as an imbalance between the peroxide-removing-related enzymes glutathione peroxidase/glutathione reductase activities in the cerebral cortex. These findings indicate a significant relationship between hypercholesterolemia, cognitive impairment, and cortico-cerebral mitochondrial dysfunctional/oxidative stress. Because of the involvement of such alterations in AD patients, our data render this mouse model of hypercholesterolemia a useful approach to comprehend the molecular events mediating AD pathogenesis. |
