title: A role for hippocampal PSA-NCAM and NMDA-NR2B receptor function in flavonoid-induced spatial memory improvements in young rats.
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.
authors: 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.
authors: Catarina
authors: C
authors: Rendeiro
authors: Berand Neuropharmacology, NovaUCD, Belfield Innovation Park, UCD, Belfield, Dublin 4, Ireland.
authors: Andrew
authors: A
authors: Foley
authors: Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading RG6 6AP, UK.
authors: Vera C
authors: VC
authors: Lau
authors: School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
authors: Rebecca
authors: R
authors: Ring
authors: Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading RG6 6AP, UK.
authors: Ana
authors: A
authors: Rodriguez-Mateos
authors: Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading RG6 6AP, UK.
authors: David
authors: D
authors: Vauzour
authors: School of Psychology and Clinical Language Sciences, University of Reading, Reading RG6 6AL, UK.
authors: Claire M
authors: CM
authors: Williams
authors: Berand Neuropharmacology, NovaUCD, Belfield Innovation Park, UCD, Belfield, Dublin 4, Ireland; School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
authors: Ciaran
authors: C
authors: Regan
authors: Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading RG6 6AP, UK. Electronic address: j.p.e.spencer@reading.ac.uk.
authors: Jeremy P E
authors: JP
authors: Spencer
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism; D005419:Flavonoids / Q000627:therapeutic use*; D006624:Hippocampus / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000178:diet therapy* / Q000378:metabolism; D008570:Memory, Short-Term / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism*; D013028:Space Perception / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D003598:Cytoskeletal Proteins; D005419:Flavonoids; C121001:NR2B NMDA receptor; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D012794:Sialic Acids; C092069:activity regulated cytoskeletal-associated protein; C103469:polysialyl neural cell adhesion molecule; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: BDNF; Flavonoid; Hippocampus; Learning; Memory; NMDR2B; PSA-NCAM