title: 27-Hydroxycholesterol contributes to disruptive effects on learning and memory by modulating cholesterol metabolism in the rat brain.
abstract: 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-α (LXR-α) 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.
authors.affiliation: School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: D-D
authors.initials: DD
authors.lastname: Zhang
authors.affiliation: School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: H-L
authors.initials: HL
authors.lastname: Yu
authors.affiliation: School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: W-W
authors.initials: WW
authors.lastname: Ma
authors.affiliation: School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Q-R
authors.initials: QR
authors.lastname: Liu
authors.affiliation: School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: J
authors.initials: J
authors.lastname: Han
authors.affiliation: School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. Electronic address: xiaor22@ccmu.edu.cn.
authors.forename: R
authors.initials: R
authors.lastname: Xiao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006888:Hydroxycholesterols / Q000633:toxicity*; D006937:Hypercholesterolemia / Q000473:pathology / Q000523:psychology; D000960:Hypolipidemic Agents / Q000633:toxicity*; D007150:Immunohistochemistry; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D065853:Spatial Learning / Q000187:drug effects* / Q000502:physiology; D065852:Spatial Memory / Q000187:drug effects* / Q000502:physiology
chemical_list: D006888:Hydroxycholesterols; D000960:Hypolipidemic Agents; D012333:RNA, Messenger; C076996:27-hydroxycholesterol; D002784:Cholesterol
keywords: 27-hydroxycholesterol; ABCA1; HMG-CR; LXR-α; cholesterol metabolism; cognitive