title: Diffusion of docosahexaenoic and eicosapentaenoic acids through the blood-brain barrier: An in situ cerebral perfusion study.
abstract: Docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids are n-3 polyunsaturated fatty acids with a therapeutic potential for CNS diseases. Here, using an in situ brain perfusion technique in mice, we show that [(14)C]-DHA and [(14)C]-EPA readily cross the mouse blood-brain barrier (BBB) with brain transport coefficients (Clup) of 48+/-3microlg(-1)s(-1) and 52+/-4microlg(-1)s(-1), respectively. Mechanical capillary depletion of brain homogenates showed that less than 10% of [(14)C]-DHA or [(14)C]-EPA remained in endothelial cells of the brain vasculature, demonstrating that both molecules fully crossed the BBB. Addition of bovine serum albumin decreased the Clup of [(14)C]-DHA to 0.6+/-0.3microlg(-1)s(-1), indicating that binding to albumin reduced importantly, but not totally, the passage of DHA through the BBB. The Clup of [(14)C]-DHA or [(14)C]-EPA was not saturable at concentration up to 100microM, suggesting that these compounds crossed the BBB by simple diffusion. However, long-term high-DHA dietary consumption reduced the Clup of [(14)C]-DHA to 33+/-6microlg(-1)s(-1) (-20%, p<0.01). These results confirm that the brain uptake of DHA or EPA perfused with a physiological buffer is comparable to highly diffusible drugs like diazepam, and can be modulated by albumin binding and chronic dietary DHA intake.
authors.affiliation: Laval University, Quebec, QC, Canada.
authors.forename: Melissa
authors.initials: M
authors.lastname: Ouellet
authors.forename: Vincent
authors.initials: V
authors.lastname: Emond
authors.forename: Chuck T
authors.initials: CT
authors.lastname: Chen
authors.forename: Carl
authors.initials: C
authors.lastname: Julien
authors.forename: Fanchon
authors.initials: F
authors.lastname: Bourasset
authors.forename: Salvatore
authors.initials: S
authors.lastname: Oddo
authors.forename: Frank
authors.initials: F
authors.lastname: LaFerla
authors.forename: Richard P
authors.initials: RP
authors.lastname: Bazinet
authors.forename: Frédéric
authors.initials: F
authors.lastname: Calon
mesh_terms: D000465:Algorithms; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001923:Brain Chemistry / Q000502:physiology; D002196:Capillaries / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D004032:Diet; D004281:Docosahexaenoic Acids / Q000493:pharmacokinetics*; D015118:Eicosapentaenoic Acid / Q000493:pharmacokinetics*; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010477:Perfusion
chemical_list: D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid