A role for hippocampal PSA-NCAM and NMDA-NR2B receptor function in flavonoid-induced spatial memory improvements in young rats

Research output: Contribution to journalArticlepeer-review

Authors

  • Andrew Foley
  • Vera C Lau
  • Rebecca Ring
  • Ana Rodriguez-Mateos
  • David Vauzour
  • Claire M Williams
  • Ciaran Regan
  • Jeremy P E Spencer

Colleges, School and Institutes

External organisations

  • Berand Neuropharmacology, NovaUCD, Belfield Innovation Park, UCD, Belfield, Dublin 4, Ireland.
  • Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading RG6 6AP, UK.
  • School of Psychology and Clinical Language Sciences, University of Reading, Reading RG6 6AL, UK.

Abstract

The increase in incidence and prevalence of neurodegenerative diseases highlights the need for a more comprehensive understanding of how food components may affect neural systems. In particular, flavonoids have been recognized as promising agents capable of influencing different aspects of synaptic plasticity resulting in improvements in memory and learning in both animals and humans. Our previous studies highlight the efficacy of flavonoids in reversing memory impairments in aged rats, yet little is known about the effects of these compounds in healthy animals, particularly with respect to the molecular mechanisms by which flavonoids might alter the underlying synaptic modifications responsible for behavioral changes. We demonstrate that a 3-week intervention with two dietary doses of flavonoids (Dose I: 8.7 mg/day and Dose II: 17.4 mg/day) facilitates spatial memory acquisition and consolidation (24 recall) (p < 0.05) in young healthy rats. We show for the first time that these behavioral improvements are linked to increased levels in the polysialylated form of the neural adhesion molecule (PSA-NCAM) in the dentate gyrus (DG) of the hippocampus, which is known to be required for the establishment of durable memories. We observed parallel increases in hippocampal NMDA receptors containing the NR2B subunit for both 8.7 mg/day (p < 0.05) and 17.4 mg/day (p < 0.001) doses, suggesting an enhancement of glutamate signaling following flavonoid intervention. This is further strengthened by the simultaneous modulation of hippocampal ERK/CREB/BDNF signaling and the activation of the Akt/mTOR/Arc pathway, which are crucial in inducing changes in the strength of hippocampal synaptic connections that underlie learning. Collectively, the present data supports a new role for PSA-NCAM and NMDA-NR2B receptor on flavonoid-induced improvements in learning and memory, contributing further to the growing body of evidence suggesting beneficial effects of flavonoids in cognition and brain health.

Details

Original languageEnglish
Pages (from-to)335-344
Number of pages10
JournalNeuropharmacology
Volume79
Early online date11 Dec 2013
Publication statusPublished - 1 Apr 2014

Keywords

  • Animals, Brain-Derived Neurotrophic Factor, Cyclic AMP Response Element-Binding Protein, Cytoskeletal Proteins, Dentate Gyrus, Flavonoids, Hippocampus, MAP Kinase Signaling System, Male, Maze Learning, Memory Disorders, Memory, Short-Term, Nerve Tissue Proteins, Neural Cell Adhesion Molecule L1, Proto-Oncogene Proteins c-akt, Rats, Rats, Wistar, Receptors, AMPA, Receptors, N-Methyl-D-Aspartate, Sialic Acids, Space Perception, TOR Serine-Threonine Kinases, Journal Article, Research Support, Non-U.S. Gov't, memory, learning, flavonoid, BDNF, PSA-NCAM, NMDR2B