期刊
NEUROBIOLOGY OF AGING
卷 30, 期 3, 页码 407-419出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2007.07.006
关键词
Cholesterol; HDL; alpha-Tocopherol; Scavenger receptors; Lipid metabolism; Atherosclerosis; Late-onset Alzheimer's disease; LTP; Recognition memory; Spatial memory
资金
- Burke-Cornell Medical Research Institute
- NIH
- NYU
- American Federation for Aging Research
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [P01AI073693] Funding Source: NIH RePORTER
Dysregulated cholesterol metabolism is a major risk factor for atherosclerosis and other late-onset disorders, such as Alzheimer's disease. The scavenger receptor, class B, type I (SR-BI) is critical in maintaining the homeostasis of cholesterol and alpha-tocopherol. SR-BI binds high-density lipoproteins (HDL) and mediates the selective transfer of cholesteryl esters and alpha-tocopherol from circulating HDL to cells. SR-BI is also involved in reverse cholesterol transport from peripheral tissues into the liver. Previous studies using SR-BI genetic knockout mice indicated that the deletion of SR-BI resulted in an accelerated onset of atherosclerosis. We hypothesized that SR-BI-dependent lipid dysregulation might disrupt brain function leading to cognitive impairment. Here, we report that very old SR-BI knockout mice show deficient synaptic plasticity (long-term potentiation) in the CA 1 region of the hippocampus. Very old SR-BI KO mice also display selective impairments in recognition memory and spatial memory. Thus, SR-BI influences neural and cognitive processes, a finding that highlights the contribution of cholesterol and alpha-tocopherol homeostasis in proper cognitive function. (C) 2007 Elsevier Inc. All rights reserved.
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