EPA/DHA and vitamin A supplementation improves spatial memory and alleviates the age-related decrease in hippocampal RXRγ and kinase expression in rats

• Main Authors: Anne eLétondor, Benjamin eBuaud, Carole eVaysse, Emmanuel eRichard, Sophie eLaye, Véronique ePallet, Serge eAlfos
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2016-05-01
• Series: Frontiers in Aging Neuroscience
• Subjects: Hippocampus; Vitamin A; spatial memory; kinases; Retinoid receptors; n-3 long-chain PUFA
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fnagi.2016.00103/full

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.