Age-related influence of the HDL receptor SR-BI on synaptic plasticity and cognition
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Date
2009
Journal Title
Journal ISSN
Volume Title
Publisher
ELSEVIER SCIENCE INC
Abstract
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.
Description
Keywords
Cholesterol, HDL, alpha-Tocopherol, Scavenger receptors, Lipid metabolism, Atherosclerosis, Late-onset Alzheimer's disease, LTP, Recognition memory, Spatial memory, HIGH-DENSITY-LIPOPROTEIN, LONG-TERM POTENTIATION, ALPHA-TOCOPHEROL METABOLISM, CORONARY-ARTERY-DISEASE, ALZHEIMERS-DISEASE, SCAVENGER RECEPTOR, APOLIPOPROTEIN-E, NERVOUS-SYSTEM, DEFICIENT MICE, MOUSE MODEL