29
views
0
recommends
+1 Recommend
0 collections
    2
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      EPA/DHA and Vitamin A Supplementation Improves Spatial Memory and Alleviates the Age-related Decrease in Hippocampal RXRγ and Kinase Expression in Rats

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references62

          • Record: found
          • Abstract: found
          • Article: not found

          Nuclear Receptors, RXR, and the Big Bang.

          Isolation of genes encoding the receptors for steroids, retinoids, vitamin D, and thyroid hormone and their structural and functional analysis revealed an evolutionarily conserved template for nuclear hormone receptors. This discovery sparked identification of numerous genes encoding related proteins, termed orphan receptors. Characterization of these orphan receptors and, in particular, of the retinoid X receptor (RXR) positioned nuclear receptors at the epicenter of the "Big Bang" of molecular endocrinology. This Review provides a personal perspective on nuclear receptors and explores their integrated and coordinated signaling networks that are essential for multicellular life, highlighting the RXR heterodimer and its associated ligands and transcriptional mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Opposing effects of retinoic acid on cell growth result from alternate activation of two different nuclear receptors.

            Transcriptional activation of the nuclear receptor RAR by retinoic acid (RA) often leads to inhibition of cell growth. However, in some tissues, RA promotes cell survival and hyperplasia, activities that are unlikely to be mediated by RAR. Here, we show that, in addition to functioning through RAR, RA activates the "orphan" nuclear receptor PPARbeta/delta, which, in turn, induces the expression of prosurvival genes. Partitioning of RA between the two receptors is regulated by the intracellular lipid binding proteins CRABP-II and FABP5. These proteins specifically deliver RA from the cytosol to nuclear RAR and PPARbeta/delta, respectively, thereby selectively enhancing the transcriptional activity of their cognate receptors. Consequently, RA functions through RAR and is a proapoptotic agent in cells with high CRABP-II/FABP5 ratio, but it signals through PPARbeta/delta and promotes survival in cells that highly express FABP5. Opposing effects of RA on cell growth thus emanate from alternate activation of two different nuclear receptors.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Gene microarrays in hippocampal aging: statistical profiling identifies novel processes correlated with cognitive impairment.

              Gene expression microarrays provide a powerful new tool for studying complex processes such as brain aging. However, inferences from microarray data are often hindered by multiple comparisons, small sample sizes, and uncertain relationships to functional endpoints. Here we sought gene expression correlates of aging-dependent cognitive decline, using statistical profiling of gene microarrays in well powered groups of young, mid-aged, and aged rats (n = 10 per group). Animals were trained on two memory tasks, and the hippocampal CA1 region of each was analyzed on an individual microarray (one chip per animal). Aging- and cognition-related genes were identified by testing each gene by ANOVA (for aging effects) and then by Pearson's test (correlating expression with memory). Genes identified by this algorithm were associated with several phenomena known to be aging-dependent, including inflammation, oxidative stress, altered protein processing, and decreased mitochondrial function, but also with multiple processes not previously linked to functional brain aging. These novel processes included downregulated early response signaling, biosynthesis and activity-regulated synaptogenesis, and upregulated myelin turnover, cholesterol synthesis, lipid and monoamine metabolism, iron utilization, structural reorganization, and intracellular Ca2+ release pathways. Multiple transcriptional regulators and cytokines also were identified. Although most gene expression changes began by mid-life, cognition was not clearly impaired until late life. Collectively, these results suggest a new integrative model of brain aging in which genomic alterations in early adulthood initiate interacting cascades of decreased signaling and synaptic plasticity in neurons, extracellular changes, and increased myelin turnover-fueled inflammation in glia that cumulatively induce aging-related cognitive impairment.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Aging Neurosci
                Front Aging Neurosci
                Front. Aging Neurosci.
                Frontiers in Aging Neuroscience
                Frontiers Media S.A.
                1663-4365
                09 May 2016
                2016
                : 8
                : 103
                Affiliations
                [1] 1Université de Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286 Bordeaux, France
                [2] 2INRA, Nutrition et Neurobiologie Intégrée, UMR 1286 Bordeaux, France
                [3] 3Bordeaux INP, Nutrition et Neurobiologie Intégrée, UMR 1286 Bordeaux, France
                [4] 4ITERG, Institut des Corps Gras Pessac, France
                [5] 5INSERM, Biothérapie des Maladies Génétiques Inflammatoires et Cancers, U1035 Bordeaux, France
                Author notes

                Edited by: Elizabeth J. Johnson, Tufts University, USA

                Reviewed by: Kathy R. Magnusson, Oregon State University, USA; Cathy W. Levenson, Florida State University College of Medicine, USA; Simon C. Dyall, Bournemouth University, UK

                *Correspondence: Serge Alfos, serge.alfos@ 123456enscbp.fr

                These authors have contributed equally to this work.

                Article
                10.3389/fnagi.2016.00103
                4860397
                27242514
                8d393452-12a2-4b2a-ae82-408bd15ea355
                Copyright © 2016 Létondor, Buaud, Vaysse, Richard, Layé, Pallet and Alfos.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 17 December 2015
                : 22 April 2016
                Page count
                Figures: 6, Tables: 4, Equations: 0, References: 70, Pages: 16, Words: 0
                Categories
                Neuroscience
                Original Research

                Neurosciences
                n-3 long-chain pufa,vitamin a,spatial memory,hippocampus,kinases,retinoid receptors
                Neurosciences
                n-3 long-chain pufa, vitamin a, spatial memory, hippocampus, kinases, retinoid receptors

                Comments

                Comment on this article