De Oliveira 2011 Neuroscience
| de Oliveira J, Hort MA, Moreira EL, Glaser V, Ribeiro-do-Valle RM, Prediger RD, Farina M, Latini A, de Bem AF (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. |
de Oliveira J, Hort MA, Moreira EL, Glaser V, Ribeiro-do-Valle RM, Prediger RD, Farina M, Latini A, De Bem Andreza Fabro (2011) Neuroscience
Abstract: 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.
• O2k-Network Lab: BR Florianapolis Latini A, BR Florianopolis De Bem AF
Labels: MiParea: Genetic knockout;overexpression
Pathology: Alzheimer's, Neurodegenerative
Stress:Oxidative stress;RONS
Organism: Mouse
Tissue;cell: Nervous system
Enzyme: Complex I, Complex II;succinate dehydrogenase
