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

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• 作者：Catarina Rendeiro^a ; ^b ; Andrew Foley^c ; Vera C. Lau^a ; Rebecca Ring^d ; Ana Rodriguez-Mateos^a ; ¹ ; David Vauzour^a ; ² ; Claire M. Williams^b ; Ciaran Regan^c ; ^d ; Jeremy P.E. Spencer^a ; ^{j.p.e.spencer@reading.ac.uk" class="auth_mail}
• 关键词：Memory ; Learning ; Flavonoid ; Hippocampus ; BDNF ; PSA-NCAM ; NMDR2B
• 刊名：Neuropharmacology
• 出版年：April, 2014
• 年：2014
• 卷：79
• 期：Complete
• 页码：335-344
• 全文大小：1217 K

文摘

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聽mg/day and Dose II: 17.4聽mg/day) facilitates spatial memory acquisition and consolidation (24 recall) (p聽<聽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聽mg/day (p聽<聽0.05) and 17.4聽mg/day (p聽<聽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.