title: Docosahexaenoic acid (22:6n-3) enrichment of membrane phospholipids increases gap junction coupling capacity in cultured astrocytes.
abstract: Although it is agreed that n-3 polyunsaturated fatty acids (PUFAs) are important for brain function, it has yet to be demonstrated how they are involved in precise cellular mechanisms. We investigated the role of enhanced n-3 PUFA in astrocyte membranes on the gap junction capacity of these cells. Astrocytes isolated from newborn rat cortices were grown in medium supplemented with docosahexaenoic acid (DHA), the main n-3 PUFA in cell membranes, or arachidonic acid (AA), the main n-6 PUFA, plus an antioxidant (alpha-tocopherol or N-acetyl-cystein) to prevent peroxidation. The resulting three populations of astrocytes differed markedly in their n-3:n-6 PUFA ratios in phosphatidylethanolamine and phosphatidylcholine, the main phospholipids in membranes. DHA-supplemented cells had a physiological high n-3:n-6 ratio (1.58), unsupplemented cells had a low n-3:n-6 ratio (0.66) and AA-supplemented cells had a very low n-3:n-6 ratio (0.36), with excess n-6 PUFA. DHA-supplemented astrocytes had a greater gap junction capacity than unsupplemented cells or AA-supplemented cells. The enhanced gap junction coupling of DHA-enriched cells was associated with a more functional distribution of connexin 43 at cell interfaces (shown by immunocytochemistry) and more of the main phosphorylated isoform of connexin 43. These findings suggest that the high n-3:n-6 PUFA ratio that occurs naturally in astrocyte membranes is needed for optimal gap junction coupling in these cells.
authors.affiliation: Unité de Nutrition et Régulation Lipidique des Fonctions Cérébrales (Nu.Re.Li.Ce), INRA, 78352 Jouy-en-Josas cedex, France.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Champeil-Potokar
authors.forename: Catherine
authors.initials: C
authors.lastname: Chaumontet
authors.forename: Philippe
authors.initials: P
authors.lastname: Guesnet
authors.forename: Monique
authors.initials: M
authors.lastname: Lavialle
authors.forename: Isabelle
authors.initials: I
authors.lastname: Denis
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D018031:Connexin 43 / Q000187:drug effects / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D018031:Connexin 43; D008563:Membrane Lipids; D010743:Phospholipids; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid