The effects of flavonoids and flavonoid-rich blueberries on memory and the mechanisms by which these effects are mediated

• Main Author: Rendeiro, Ana Catarina
• Published: University of Reading 2011
• Subjects: 613.286
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.552993

It is widely accepted that diet strongly influences the incidence and onset of both cardiovascular diseases and neurodegeneration. Recently, phytochemical-rich foods, particularly those rich in flavonoids, such as blueberries, green tea and cocoa, have been shown to have a positive impact on memory and learning and cognitive function in both animals and humans. The mechanisms by which flavonoids exert these actions on cognitive performance are starting to emerge with evidence suggesting that they may modulate the activation status of neuronal receptors, signaling proteins and gene expression in the hippocampus. In the present Thesis we further explore the mechanisms by which flavonoids, present in blueberry, affect memory and learning in both young and aged rodents and relate such changes in the brain with behavioural cognitive outcomes. We show for the first time that pure flavonoids present in blueberry, particularly the flavanol monomers (- )-epicatechin and catechin and anthocyanins, are capable of mediating improvements in spatial memory in aged animals when dosed at the same levels they are found within the blueberry. This data suggests that flavonoids are the likely causal agents that mediate the cognitive effects of blueberry in vivo. We also show a positive impact of blueberry supplementation on spatial memory in young rodents in two separate experiments using well-establlshed behavioural paradigms. Mostly importantly we found that chronic blueberry intervention causes an up-regulation of hippocampal BDNF at protein level and at mRNA level in both young and aged animals, reinforcing the importance of this neurotrophin in the blueberry- induced learning and memory improvements. A more detailed analysis of the mechanisms underlying the impact of flavonoid-rich blueberries on memory revealed an increase in PSA-NCAM positive neurons in the dentate gyrus which is known to mediate synaptic transmission and neuronal remodeling. Further increases in NR2B-containing NMDR receptors in the hippocampus correlate with up-regulation with PSA-NCAM, suggesting an enhancement of synaptic plasticity, likely to be driven by an increase in glutamate signaling. As such, these changes seem to be mediated by central signaling pathways utilized in learning processes, notably ERK-CREB-BDNF and Akt-mTOR-ARC. Overall, our results provide further support for the impact of flavonoid-rich blueberries on learning performance in aged rodents as well as in young healthy rodents, suggesting a potential mechanism by which flavonoids act in the brain.