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, 2011 Dec 01.
Article
in En
| MEDLINE
| ID: mdl-21945034
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. LDLrâ»/â» mice displayed spatial learning and memory impairments regardless of diet. Moreover, LDLrâ»/â» 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 LDLrâ»/â» 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain
/
Cognition Disorders
/
Oxidative Stress
/
Hypercholesterolemia
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Neuroscience
Year:
2011
Document type:
Article
Affiliation country:
Brasil