title: Transgenic increase in n-3/n-6 fatty acid ratio protects against cognitive deficits induced by an immune challenge through decrease of neuroinflammation.
abstract: Polyunsaturated fatty acids (PUFAs) display immunomodulatory properties in the brain, n-3 PUFAs being able to reduce inflammation whereas n-6 PUFAs are more pro-inflammatory. It has been extensively demonstrated that exposure to a peripheral immune challenge leads to the production and release of inflammatory mediators in the brain in association with cognitive deficits. The question arises whether n-3 PUFA supplementation could downregulate the brain inflammatory response and subsequent cognitive alterations. In this study, we used a genetically modified mouse line carrying the fat-1 gene from the roundworm Caenorhabditis elegans, encoding an n-3 PUFA desaturase that catalyzes conversion of n-6 into n-3 PUFA. Consequently, these mice display endogenously elevated n-3 PUFA tissue contents. Fat-1 mice or wild-type (WT) littermates were injected peripherally with lipopolysaccharide (LPS), a bacterial endotoxin, to induce an inflammatory episode. Our results showed that LPS altered differently the phenotype of microglia and the expression of cytokines and chemokines in Fat-1 and WT mice. In Fat-1 mice, pro-inflammatory factors synthesis was lowered compared with WT mice, whereas anti-inflammatory mechanisms were favored 24 h after LPS treatment. Moreover, LPS injection impaired spatial memory in WT mice, whereas interestingly, the Fat-1 mice showed normal cognitive performances. All together, these data suggest that the central n-3 PUFA increase observed in Fat-1 mice modulated the brain innate immune system activity, leading to the protection of animals against LPS-induced pro-inflammatory cytokine production and subsequent spatial memory alteration.
authors.affiliation: 1] INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France [2] Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Delpech
authors.affiliation: 1] INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France [2] Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Madore
authors.affiliation: 1] INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France [2] Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Joffre
authors.affiliation: 1] INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France [2] Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Aubert
authors.affiliation: Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Jing Xuan
authors.initials: JX
authors.lastname: Kang
authors.affiliation: 1] INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France [2] Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Nadjar
authors.affiliation: 1] INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France [2] Univ. Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Layé
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000235:genetics; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D055809:Illness Behavior / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology; D010641:Phenotype; D065852:Spatial Memory / Q000187:drug effects
chemical_list: D029742:Caenorhabditis elegans Proteins; D016207:Cytokines; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C466741:fat-1 protein, C elegans; D044943:Fatty Acid Desaturases