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

Williams, C. M. ORCID:, El Mohsen, M. A., Vauzour, D., Rendeiro, C., Butler, L. T., Ellis, J. A., Whiteman, M. and Spencer, J. P. E. (2008) Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels. Free Radical Biology and Medicine, 45 (3). pp. 295-305. ISSN 1873-4596

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To link to this item DOI: 10.1016/j.freeradbiomed.2008.04.008


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. (c) 2008 Elsevier Inc. All Fights reserved.

Item Type:Article
Divisions:Life Sciences > School of Psychology and Clinical Language Sciences
ID Code:13814
Uncontrolled Keywords:Animals Blotting, Western *Blueberry Plant Brain-Derived Neurotrophic Factor/*metabolism Cyclic AMP Response Element-Binding Protein/*metabolism *Diet Hippocampus/*physiology Immunoassay Male Maze Learning/physiology Memory/*physiology Mitogen-Activated Protein Kinase 3/metabolism Phosphorylation Protein Kinases/metabolism Proto-Oncogene Proteins c-akt/metabolism Rats TOR Serine-Threonine Kinases
Additional Information:Williams, Claire M El Mohsen, Manal Abd Vauzour, David Rendeiro, Catarina Butler, Laurie T Ellis, Judi A Whiteman, Matthew Spencer, Jeremy P E BB/C518222/1/Biotechnology and Biological Sciences Research Council/United Kingdom BB/F008953/1/Biotechnology and Biological Sciences Research Council/United Kingdom G0400278/N102/Medical Research Council/United Kingdom Research Support, Non-U.S. Gov't United States Free radical biology & medicine Free Radic Biol Med. 2008 Aug 1;45(3):295-305. Epub 2008 May 5.

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