Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels

Research output: Contribution to journalArticle


  • Claire M Williams
  • Manal Abd El Mohsen
  • David Vauzour
  • Laurie T Butler
  • Judi A Ellis
  • Matthew Whiteman
  • Jeremy P E Spencer

Colleges, School and Institutes

External organisations

  • School of Psychology and Clinical Language Sciences, University of Reading, Reading RG2 6AP, UK.


Phytochemical-rich foods have been shown to be effective at reversing age-related deficits in memory in both animals and humans. We show that a supplementation with a blueberry diet (2% w/w) for 12 weeks improves the performance of aged animals in spatial working memory tasks. This improvement emerged within 3 weeks and persisted for the remainder of the testing period. Memory performance correlated well with the activation of cAMP-response element-binding protein (CREB) and increases in both pro- and mature levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. Changes in CREB and BDNF in aged and blueberry-supplemented animals were accompanied by increases in the phosphorylation state of extracellular signal-related kinase (ERK1/2), rather than that of calcium calmodulin kinase (CaMKII and CaMKIV) or protein kinase A. Furthermore, age and blueberry supplementation were linked to changes in the activation state of Akt, mTOR, and the levels of Arc/Arg3.1 in the hippocampus, suggesting that pathways involved in de novo protein synthesis may be involved. Although causal relationships cannot be made among supplementation, behavior, and biochemical parameters, the measurement of anthocyanins and flavanols in the brain following blueberry supplementation may indicate that changes in spatial working memory in aged animals are linked to the effects of flavonoids on the ERK-CREB-BDNF pathway.


Original languageEnglish
Pages (from-to)295-305
Number of pages11
JournalFree Radical Biology and Medicine
Issue number3
Publication statusPublished - 1 Aug 2008


  • Animals, Blotting, Western, Blueberry Plants, Brain-Derived Neurotrophic Factor, Cyclic AMP Response Element-Binding Protein, Diet, Hippocampus, Immunoassay, Male, Maze Learning, Memory, Mitogen-Activated Protein Kinase 3, Phosphorylation, Protein Kinases, Proto-Oncogene Proteins c-akt, Rats, TOR Serine-Threonine Kinases, Journal Article, Research Support, Non-U.S. Gov't