title: EPA/DHA and Vitamin A Supplementation Improves Spatial Memory and Alleviates the Age-related Decrease in Hippocampal RXRγ and Kinase Expression in Rats.
abstract: Studies suggest that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and vitamin A are critical to delay aged-related cognitive decline. These nutrients regulate gene expression in the brain by binding to nuclear receptors such as the retinoid X receptors (RXRs) and the retinoic acid receptors (RARs). Moreover, EPA/DHA and retinoids activate notably kinase signaling pathways such as AKT or MAPK, which includes ERK1/2. This suggests that these nutrients may modulate brain function in a similar way. Therefore, we investigated in middle-aged rats the behavioral and molecular effects of supplementations with EPA/DHA and vitamin A alone or combined. 18-month-old rats exhibited reference and working memory deficits in the Morris water maze, associated with a decrease in serum vitamin A and hippocampal EPA/DHA contents. RARα, RXRβ, and RXRγ mRNA expression and CAMKII, AKT, ERK1/2 expression were decreased in the hippocampus of middle-aged rats. A combined EPA/DHA and vitamin A supplementation had a beneficial additive effect on reference memory but not in working memory in middle-aged rats, associated with an alleviation of the age-related decrease in RXRγ, CAMKII, AKT, and ERK1 expression in the hippocampus. This study provides a new combined nutritional strategy to delay brain aging.
authors.affiliation: Université de Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286Bordeaux, France; INRA, Nutrition et Neurobiologie Intégrée, UMR 1286Bordeaux, France; Bordeaux INP, Nutrition et Neurobiologie Intégrée, UMR 1286Bordeaux, France; ITERG, Institut des Corps GrasPessac, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Létondor
authors.affiliation: ITERG, Institut des Corps Gras Pessac, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Buaud
authors.affiliation: ITERG, Institut des Corps Gras Pessac, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Vaysse
authors.affiliation: INSERM, Biothérapie des Maladies Génétiques Inflammatoires et Cancers, U1035 Bordeaux, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Richard
authors.affiliation: Université de Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286Bordeaux, France; INRA, Nutrition et Neurobiologie Intégrée, UMR 1286Bordeaux, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Layé
authors.affiliation: Université de Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286Bordeaux, France; INRA, Nutrition et Neurobiologie Intégrée, UMR 1286Bordeaux, France; Bordeaux INP, Nutrition et Neurobiologie Intégrée, UMR 1286Bordeaux, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Pallet
authors.affiliation: Université de Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286Bordeaux, France; INRA, Nutrition et Neurobiologie Intégrée, UMR 1286Bordeaux, France; Bordeaux INP, Nutrition et Neurobiologie Intégrée, UMR 1286Bordeaux, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Alfos
keywords: hippocampus; kinases; n-3 long-chain PUFA; retinoid receptors; spatial memory; vitamin A