Age-related influence of the HDL receptor SR-BI on synaptic plasticity and cognition

NEUROBIOLOGY OF AGING

卷:30

Article

Chang, Eric H.^1,3  Rigotti, Attilio²  Huerta, Patricio T.¹ 

[1] Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, BurkeCornell Med Res Inst, White Plains, NY 10605 USA

[2] Pontificia Univ Catolica Chile, Fac Med, Dept Gastroenterol, Santiago, Chile

[3] NYU, Ctr Neural Sci, New York, NY 10003 USA

关键词: Cholesterol;    HDL;    alpha-Tocopherol;    Scavenger receptors;    Lipid metabolism;    Atherosclerosis;    Late-onset Alzheimer's disease;    LTP;    Recognition memory;    Spatial memory;   

DOI  :  10.1016/j.neurobiolaging.2007.07.006

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free