Age-related influence of the HDL receptor SR-BI on synaptic plasticity and cognition
Age-related influence of the HDL receptor SR-BI on synaptic plasticity and cognition
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DOI：
10.1016/j.neurobiolaging.2007.07.006
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发表时间：
2009-03-01
影响因子：
4.2
通讯作者：
Huerta, Patricio T.
中科院分区：
文献类型：
--
作者：
Chang, Eric H.;Rigotti, Attilio;Huerta, Patricio T.
胆固醇代谢失调是动脉粥样硬化和其他迟发性疾病（例如阿尔茨海默病）的主要危险因素。 B 类 I 型清道夫受体 (SR-BI) 对于维持胆固醇和 α-生育酚的稳态至关重要。 SR-BI 结合高密度脂蛋白 (HDL)，并介导胆固醇酯和 α-生育酚从循环 HDL 选择性转移至细胞。 SR-BI 还参与胆固醇从外周组织反向转运至肝脏。先前使用SR-BI基因敲除小鼠的研究表明，SR-BI的缺失会导致动脉粥样硬化的加速发生。我们假设 SR-BI 依赖性脂质失调可能会破坏大脑功能，导致认知障碍。在这里，我们报告说，非常老的 SR-BI 敲除小鼠在海马 CA 1 区域表现出突触可塑性（长期增强）缺陷。非常老的 SR-BI KO 小鼠也表现出识别记忆和空间记忆的选择性损伤。因此，SR-BI 影响神经和认知过程，这一发现强调了胆固醇和 α-生育酚稳态对正常认知功能的贡献。 (C) 2007 Elsevier Inc. 保留所有权利。
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.