title: Dietary n-3 PUFAs Deficiency Increases Vulnerability to Inflammation-Induced Spatial Memory Impairment.
abstract: Dietary n-3 polyunsaturated fatty acids (PUFAs) are critical components of inflammatory response and memory impairment. However, the mechanisms underlying the sensitizing effects of low n-3 PUFAs in the brain for the development of memory impairment following inflammation are still poorly understood. In this study, we examined how a 2-month n-3 PUFAs deficiency from pre-puberty to adulthood could increase vulnerability to the effect of inflammatory event on spatial memory in mice. Mice were given diets balanced or deficient in n-3 PUFAs for a 2-month period starting at post-natal day 21, followed by a peripheral administration of lipopolysaccharide (LPS), a bacterial endotoxin, at adulthood. We first showed that spatial memory performance was altered after LPS challenge only in n-3 PUFA-deficient mice that displayed lower n-3/n-6 PUFA ratio in the hippocampus. Importantly, long-term depression (LTD), but not long-term potentiation (LTP) was impaired in the hippocampus of LPS-treated n-3 PUFA-deficient mice. Proinflammatory cytokine levels were increased in the plasma of both n-3 PUFA-deficient and n-3 PUFA-balanced mice. However, only n-3 PUFA-balanced mice showed an increase in cytokine expression in the hippocampus in response to LPS. In addition, n-3 PUFA-deficient mice displayed higher glucocorticoid levels in response to LPS as compared with n-3 PUFA-balanced mice. These results indicate a role for n-3 PUFA imbalance in the sensitization of the hippocampal synaptic plasticity to inflammatory stimuli, which is likely to contribute to spatial memory impairment.
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.|University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Delpech
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.|University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Thomazeau
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.|University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Madore
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.|University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Clementine
authors.initials: C
authors.lastname: Bosch-Bouju
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.|University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Larrieu
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.|University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Chloe
authors.initials: C
authors.lastname: Lacabanne
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.|University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Remus-Borel
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.|University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Aubert
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.|University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Joffre
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.|University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Nadjar
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.|University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Layé
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000097:blood / Q000235:genetics; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000150:complications*; D008070:Lipopolysaccharides / Q000633:toxicity; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D016622:Silver Staining
chemical_list: D016207:Cytokines; D015525:Fatty Acids, Omega-3; D008070:Lipopolysaccharides; D003345:Corticosterone