title: Gene expression of fatty acid transport and binding proteins in the blood-brain barrier and the cerebral cortex of the rat: differences across development and with different DHA brain status.
abstract: Specific mechanisms for maintaining docosahexaenoic acid (DHA) concentration in brain cells but also transporting DHA from the blood across the blood-brain barrier (BBB) are not agreed upon. Our main objective was therefore to evaluate the level of gene expression of fatty acid transport and fatty acid binding proteins in the cerebral cortex and at the BBB level during the perinatal period of active brain DHA accretion, at weaning, and until the adult age. We measured by real time RT-PCR the mRNA expression of different isoforms of fatty acid transport proteins (FATPs), long-chain acyl-CoA synthetases (ACSLs), fatty acid binding proteins (FABPs) and the fatty acid transporter (FAT)/CD36 in cerebral cortex and isolated microvessels at embryonic day 18 (E18) and postnatal days 14, 21 and 60 (P14, P21 and P60, respectively) in rats receiving different n-3 PUFA dietary supplies (control, totally deficient or DHA-supplemented). In control rats, all the genes were expressed at the BBB level (P14 to P60), the mRNA levels of FABP5 and ACSL3 having the highest values. Age-dependent differences included a systematic decrease in the mRNA expressions between P14-P21 and P60 (2 to 3-fold), with FABP7 mRNA abundance being the most affected (10-fold). In the cerebral cortex, mRNA levels varied differently since FATP4, ACSL3 and ACSL6 and the three FABPs genes were highly expressed. There were no significant differences in the expression of the 10 genes studied in n-3 deficient or DHA-supplemented rats despite significant differences in their brain DHA content, suggesting that brain DHA uptake from the blood does not necessarily require specific transporters within cerebral endothelial cells and could, under these experimental conditions, be a simple passive diffusion process.
authors.affiliation: INRA, Nutrition et Régulation Lipidique des Fonctions Cérébrales, 78352 Jouy-en-Josas, France. Electronic address: helene.pelerin@sfr.fr.
authors.forename: Hélène
authors.initials: H
authors.lastname: Pélerin
authors.affiliation: INRA, Nutrition et Régulation Lipidique des Fonctions Cérébrales, 78352 Jouy-en-Josas, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Jouin
authors.affiliation: INRA, Nutrition et Régulation Lipidique des Fonctions Cérébrales, 78352 Jouy-en-Josas, France.
authors.forename: Marie-Sylvie
authors.initials: MS
authors.lastname: Lallemand
authors.affiliation: INRA, Nutrition et Régulation Lipidique des Fonctions Cérébrales, 78352 Jouy-en-Josas, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Alessandri
authors.affiliation: Research Center on Aging, and Department of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada J1H 4C4C.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Cunnane
authors.affiliation: INRA, Nutrition et Régulation Lipidique des Fonctions Cérébrales, 78352 Jouy-en-Josas, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Langelier
authors.affiliation: PG Consulting, 13 villa Bellevue 91440 Bures sur Yvette, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Guesnet
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000254:growth & development / Q000378:metabolism*; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000235:genetics* / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics; D050612:Fatty Acid Transport Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000378:metabolism; D005786:Gene Expression Regulation; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats
chemical_list: D050612:Fatty Acid Transport Proteins; D050556:Fatty Acid-Binding Proteins; D015525:Fatty Acids, Omega-3; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids
keywords: Blood-brain barrier; Brain; DHA status; Development; Fatty acid transport proteins; Long-chain polyunsaturated fatty acids