title: Direct evidence of abca1-mediated efflux of cholesterol at the mouse blood-brain barrier.
abstract: We investigated the expression and function of Abca1 in wild-type C57BL/6, abca1(+/+), and abca1(-/-) mice brain capillaries forming the blood-brain barrier (BBB). We first demonstrated by quantitative RT-PCR and Western immunoblot that Abca1 was expressed and enriched in the wild-type mouse brain capillaries. In abca1(-/-) mice, we reported that the lack of Abca1 resulted in an 1.6-fold increase of the Abcg4 expression level compared to abca1(+/+) mice. Next, using the in situ brain perfusion technique, we showed that the [(3)H]cholesterol brain uptake clearance (Cl(up), μl/s/g brain), was significantly increased (107%) in abca1(-/-) mice compared to abca1(+/+) mice, meaning that the deficiency of Abca1 conducted to a significant decrease of the cholesterol efflux at the BBB level. In addition, the co-perfusion of probucol (Abca1 inhibitor) with [(3)H]cholesterol resulted in an increase of [(3)H]cholesterol Cl(up) (115%) in abca1(+/+) but not in abca1(-/-) mice, meaning that probucol inhibited selectively the efflux function of Abca1. In conclusion, our results demonstrated that Abca1 was expressed in the mouse brain capillaries and that Abca1 functions as an efflux transporter through the mouse BBB.
authors.affiliation: Laboratory of Clinical Pharmacy, EA4123, University of Paris Sud 11, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France.
authors.forename: Tuan Minh
authors.initials: TM
authors.lastname: Do
authors.forename: Mélissa
authors.initials: M
authors.lastname: Ouellet
authors.forename: Frédéric
authors.initials: F
authors.lastname: Calon
authors.forename: Giovanna
authors.initials: G
authors.lastname: Chimini
authors.forename: Hélène
authors.initials: H
authors.lastname: Chacun
authors.forename: Robert
authors.initials: R
authors.lastname: Farinotti
authors.forename: Fanchon
authors.initials: F
authors.lastname: Bourasset
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000070996:ATP Binding Cassette Transporter, Subfamily G; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000601:surgery; D002784:Cholesterol / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011341:Probucol / Q000494:pharmacology
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000070996:ATP Binding Cassette Transporter, Subfamily G; D018528:ATP-Binding Cassette Transporters; C486685:Abcg4 protein, mouse; D002784:Cholesterol; D011341:Probucol