The Effect of 24-Hydroxy Cholesterol on Production of Reactive Oxygen Species (ROS) in Cultured Astrocytes Treated by Beta Amyloid

Alzheimer's disease is a neurodegenerative disorder characterized by the accumulation of beta-amyloid plaques outside the cells, and intracellular hyperphosphorylation of tau protein. Amyloid beta is involved in both the pathogenesis of Alzheimer's disease and induction of reactive oxygen species (ROS). Since 24-hydroxy cholesterol (24-OHCho) as a polar metabolite can eliminate excess cholesterol in the brain, we investigated the regulatory role of 24-hydroxy cholesterol on the level of reactive oxygen species induced by exogenous cholesterol and amyloid beta.
Astrocytes were isolated from the brain of newborn C57BL/6 mice, and cultured in Dulbecco's modified Eagle's medium (DMEM) 10% fetal bovine serum (FBS). Intracellular reactive oxygen species were measured in cells treated with various concentration of cholesterol by fluorimeter, and also in the presence of beta amyloid with or without of 24-hydroxy cholesterol. Results were analyzed using ANOVA test via SPSS software.
Findings: The production of reactive oxygen species was significantly increased when astrocytes were treated with exogenous cholesterol or amyloid beta, compare to control. However, treating with 24-hydroxy cholesterol significantly decreased the level of reactive oxygen species in beta-amyloid group.
Based on various reports, beta-amyloid increases cholesterol levels in patients with Alzheimer’s disease. On the other hand, 24-hydroxy cholesterol is one of the important factors in regulating cholesterol homeostasis in the brain, and plays an efficient role in reduction of intracellular generation of reactive oxygen species in the case of Alzheimer’s disease, by reduction of cholesterol.