title: Increased flux of the plant sterols campesterol and sitosterol across a disrupted blood brain barrier.
abstract: The intact blood-brain barrier in mammalians prevents exchange of cholesterol loaden particles between periphery and brain and thus nearly all cholesterol in this organ originates from de novo synthesis. Dietary cholesterol homologues from plants, campesterol and sitosterol, are known to get enriched to some extent in the mammalian brain. We recently showed that Pdgfb(ret)(/)(ret) mice, with a pericyte deficiency and a leaking blood-brain barrier phenotype, have significantly higher levels of plant sterols in the brain compared to their heterozygous Pdgfb(ret)(/)(+) controls keeping the integrity of the blood-brain barrier (BBB). In order to further study the protective functionality of the BBB we synthesized a mixture of [(2)H6]campesterol/sitosterol and fed it for 10-40days to genetically different types of animals. There was a significant enrichment of both deuterium stable isotope labeled plant sterols in the brain of both strains of mice, however, with a lower enrichment in the controls. As expected, the percentage and absolute enrichment was higher for [(2)H6]campesterol than for the more lipophilic [(2)H6]sitosterol. The results confirm that a leaking BBB causes increased flux of plant sterols into the brain. The significant flux of the labeled plant sterols into the brain of the control mice illustrates that the presence of an alkyl group in the 24-position of the steroid side chain markedly increases the ability of cholesterol to pass an intact BBB. We discuss the possibility that there is a specific transport mechanism involved in the flux of alkylated cholesterol species across the BBB.
authors: Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institute Huddinge, 14186 Huddinge, Sweden; Department of Biochemistry, Faculty of Medicine, University of Khartoum, 11111 Khartoum, Sudan.
authors: Ahmed A
authors: AA
authors: Saeed
authors: Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden.
authors: Guillem
authors: G
authors: Genové
authors: Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden.
authors: Tian
authors: T
authors: Li
authors: Institute for Clinical Chemistry and Clinical Pharmacology, University Clinics Bonn, 53105 Bonn, Germany.
authors: Frank
authors: F
authors: Hülshorst
authors: Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden.
authors: Christer
authors: C
authors: Betsholtz
authors: Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institute Huddinge, 14186 Huddinge, Sweden.
authors: Ingemar
authors: I
authors: Björkhem
authors: Institute for Clinical Chemistry and Clinical Pharmacology, University Clinics Bonn, 53105 Bonn, Germany. Electronic address: dieter.luetjohann@ukb.uni-bonn.de.
authors: Dieter
authors: D
authors: Lütjohann
mesh_terms: D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology*; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D003903:Deuterium; D013058:Mass Spectrometry; D008822:Mice, Transgenic; D010840:Phytosterols / Q000737:chemistry / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D012855:Sitosterols / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010840:Phytosterols; D020574:Proto-Oncogene Proteins c-sis; D012855:Sitosterols; C021273:campesterol; D002784:Cholesterol; D003903:Deuterium
keywords: Blood–Brain-Barrier; Brain lipids; Cholesterol metabolism; Phytosterols; Plant sterols; Stable isotopes