27-Hydroxycholesterol mediates negative effects of dietary cholesterol on cognition in mice

Abstract In spite of the fact that cholesterol does not pass the blood–brain barrier, treatment of mice with dietary cholesterol causes significant effects on a number of genes in the brain and in addition a memory impairment. We have suggested that these effects are mediated by 27-hydroxycholesterol, which is able to pass the blood–brain barrier. To test this hypothesis we utilized Cyp 27−/− mice lacking 27-hydroxycholesterol. The negative effect on memory observed after treatment of wildtype mice with dietary cholesterol was not observed in these mice. The cholesterol diet reduced the levels of the “memory protein” Arc (Activity Regulated Cytoskeleton associated protein) in the hippocampus of the wildtype mice but not in the hippocampus of the Cyp 27−/− mice. The results are consistent with 27-hydroxycholesterol as the mediator of the negative effects of cholesterol on cognition.