title: 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 Cyp27-/- 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 Cyp27-/- mice. The results are consistent with 27-hydroxycholesterol as the mediator of the negative effects of cholesterol on cognition.
authors.affiliation: Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, SE 141 86 Stockholm, Sweden.
authors.forename: Maura
authors.initials: M
authors.lastname: Heverin
authors.affiliation: Karolinska Institute, Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, 141 57 Stockholm, Sweden.
authors.forename: Silvia
authors.initials: S
authors.lastname: Maioli
authors.affiliation: Karolinska Institute, Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, 141 57 Stockholm, Sweden.
authors.forename: Therese
authors.initials: T
authors.lastname: Pham
authors.affiliation: Karolinska Institute, Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, 141 57 Stockholm, Sweden.
authors.forename: Laura
authors.initials: L
authors.lastname: Mateos
authors.affiliation: Karolinska Institute, Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, 141 57 Stockholm, Sweden.
authors.forename: Elena
authors.initials: E
authors.lastname: Camporesi
authors.affiliation: Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, SE 141 86 Stockholm, Sweden.
authors.forename: Zeina
authors.initials: Z
authors.lastname: Ali
authors.affiliation: Karolinska Institute, Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, 141 57 Stockholm, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.affiliation: Karolinska Institute, Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, 141 57 Stockholm, Sweden.
authors.forename: Angel
authors.initials: A
authors.lastname: Cedazo-Minguez
authors.affiliation: Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, SE 141 86 Stockholm, Sweden. Electronic address: ingemar.bjorkhem@karolinska.se.
authors.forename: Ingemar
authors.initials: I
authors.lastname: Björkhem
mesh_terms: D000386:AIDS-Related Complex / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D053493:Cholestanetriol 26-Monooxygenase / Q000172:deficiency / Q000235:genetics; D002784:Cholesterol / Q000009:adverse effects*; D019826:Cholic Acid / Q000008:administration & dosage; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006888:Hydroxycholesterols / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D065853:Spatial Learning / Q000187:drug effects
chemical_list: D006888:Hydroxycholesterols; D012333:RNA, Messenger; C076996:27-hydroxycholesterol; D002784:Cholesterol; D053493:Cholestanetriol 26-Monooxygenase; C506832:Cyp27a1 protein, mouse; D019826:Cholic Acid
keywords: 27-Hydroxycholesterol; Activity-regulated cytoskeleton-associated protein; Cholesterol; Hypercholesterolemia; Morris water maze; Oxysterol