27-HYDROXYCHOLESTEROL CONTRIBUTES TO DISRUPTIVE EFFECTS ON LEARNING AND MEMORY BY MODULATING CHOLESTEROL METABOLISM IN THE RAT BRAIN

被引：35
|
作者：
Zhang, D. -D. [1 ]
Yu, H. -L. [1 ]
Ma, W. -W. [1 ]
Liu, Q. -R. [1 ]
Han, J. [1 ]
Wang, H. [1 ]
Xiao, R. [1 ]
机构：
[1] Capital Med Univ, Sch Publ Hlth, Beijing Key Lab Environm Toxicol, Beijing 100069, Peoples R China
来源：
NEUROSCIENCE | 2015年 / 300卷
基金：
中国国家自然科学基金;
关键词：
27-hydroxycholesterol; cognitive; cholesterol metabolism; HMG-CR; LXR-alpha; ABCA1; ENDOPLASMIC-RETICULUM CHOLESTEROL; ALZHEIMERS-DISEASE; TRANSFER PROTEIN; OXYSTEROLS; EXPRESSION; LIVER; BETA; 24S-HYDROXYCHOLESTEROL; LIPOPROTEINS; HOMEOSTASIS;
D O I：
10.1016/j.neuroscience.2015.05.022
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Cholesterol metabolism is important for neuronal function in the central nervous system (CNS). The oxysterol 27-hydroxycholesterol (27-OHC) is a cholesterol metabolite that crosses the blood-brain-barrier (BBB) and may be a useful substitutive marker for neurodegenerative diseases. However, the effects of 27-OHC on learning and memory and the underlying mechanisms are unclear. To determine this mechanism, we investigated learning and memory and cholesterol metabolism in rat brain following the injection of various doses of 27-OHC into the caudal vein. We found that 27-OHC increased cholesterol levels and upregulated the expression of liver X receptor-alpha (LXR-alpha) and adenosine triphosphate (ATP)-binding cassette transporter protein family member A1 (ABCA1). In addition, 27-OHC decreased the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CR) and low-density lipoprotein receptor (LDLR) in rat brain tissues. These findings suggest that 27-OHC may negatively modulate cognitive effects and cholesterol metabolism in the brain. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码：163 / 173
页数：11
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