title: Efficient Docosahexaenoic Acid Uptake by the Brain from a Structured Phospholipid.
abstract: Docosahexaenoic acid (DHA) is the main essential omega-3 fatty acid in brain tissues required for normal brain development and function. An alteration of brain DHA in neurodegenerative diseases such as Alzheimer's and Parkinson's is observed. Targeted intake of DHA to the brain could compensate for these deficiencies. Blood DHA is transported across the blood-brain barrier more efficiently when esterified at the sn-2 position of lyso-phosphatidylcholine. We used a structured phosphatidylcholine to mimic 2-docosahexaenoyl-lysoPC (lysoPC-DHA), named AceDoPC (1-acetyl,2-docosahexaenoyl-glycerophosphocholine), that may be considered as a stabilized form of the physiological lysoPC-DHA and that is neuroprotective in experimental ischemic stroke. The aim of the present study was to investigate whether AceDoPC is a relevant delivery form of DHA to the brain in comparison with other forms of the fatty acid. By combining in vitro and in vivo experiments, our findings report for the first time that AceDoPC is a privileged and specific carrier of DHA to the brain, when compared with DHA-containing PC and non-esterified DHA. We also show that AceDoPC was hydrolyzed, in part, into lysoPC-DHA. Ex vivo autoradiography of rat brain reveals that DHA from AceDoPC was localized in specific brain regions playing key roles in memory, thoughts, and cognitive functions. Finally, using molecular modeling approaches, we demonstrate that electrostatic and lipophilic potentials are distributed very similarly at the surfaces of AceDoPC and lysoPC-DHA. Our findings identify AceDoPC as an efficient way to specifically target DHA to the brain, which would allow potential preventive and therapeutic approaches for neurological diseases.
authors.affiliation: INSERM UMR 1060, CarMeN laboratory, IMBL/INSA-Lyon, Université de Lyon, F-69621, Villeurbanne, France.
authors.forename: Mayssa
authors.initials: M
authors.lastname: Hachem
authors.affiliation: INSERM UMR 1060, CarMeN laboratory, IMBL/INSA-Lyon, Université de Lyon, F-69621, Villeurbanne, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Géloën
authors.affiliation: INSERM UMR 1060, CarMeN laboratory, IMBL/INSA-Lyon, Université de Lyon, F-69621, Villeurbanne, France.
authors.forename: Amanda Lo
authors.initials: AL
authors.lastname: Van
authors.affiliation: INSERM UMR 1060, CarMeN laboratory, IMBL/INSA-Lyon, Université de Lyon, F-69621, Villeurbanne, France.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Foumaux
authors.affiliation: Université d'Artois, EA2465, Lens, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Fenart
authors.affiliation: Université d'Artois, EA2465, Lens, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Gosselet
authors.affiliation: INRA UMR 203, BF2I laboratory, INSA-Lyon, Université de Lyon, F-69621, Villeurbanne, France.
authors.forename: Pedro
authors.initials: P
authors.lastname: Da Silva
authors.affiliation: Polaris, 29170, Pleuven, France.
authors.forename: Gildas
authors.initials: G
authors.lastname: Breton
authors.affiliation: INSERM UMR 1060, CarMeN laboratory, IMBL/INSA-Lyon, Université de Lyon, F-69621, Villeurbanne, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Lagarde
authors.affiliation: INSERM UMR 1060, CarMeN laboratory, IMBL/INSA-Lyon, Université de Lyon, F-69621, Villeurbanne, France.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Picq
authors.affiliation: INSERM UMR 1060, CarMeN laboratory, IMBL/INSA-Lyon, Université de Lyon, F-69621, Villeurbanne, France. nathalie.bernoud-hubac@insa-lyon.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bernoud-Hubac
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000378:metabolism; D011851:Radioactivity; D051381:Rats; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D010713:Phosphatidylcholines; D004281:Docosahexaenoic Acids
keywords: Blood–brain barrier; Brain; Docosahexaenoic acid; Lyso-phosphatidylcholine; Transport