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The Journal of Neuroscience, May 30, 2007, 27(22):5869-5878; doi:10.1523/JNEUROSCI.0914-07.2007

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Behavioral/Systems/Cognitive
Plant-Derived Flavanol (–)Epicatechin Enhances Angiogenesis and Retention of Spatial Memory in Mice

Henriette van Praag,¹ Melanie J. Lucero,¹ Gene W. Yeo,³ Kimberly Stecker,¹ Neema Heivand,¹ Chunmei Zhao,¹ Ed Yip,¹ Mia Afanador,¹ Hagen Schroeter,² John Hammerstone,² and Fred H. Gage¹

¹Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, ²Mars Incorporated, Rockville, Maryland 20850, and ³Crick-Jacobs Center for Theoretical and Computational Biology, The Salk Institute for Biological Studies, La Jolla, California 92037

Correspondence should be addressed to Dr. Fred H. Gage, Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037. Email: gage{at}salk.edu

Diet and exercise have a profound impact on brain function. In particular, natural nutrients found in plants may influence neuronal survival and plasticity. Here, we tested whether consumption of a plant-derived flavanol, (–)epicatechin, enhances cognition in sedentary or wheel-running female C57BL/6 mice. Retention of spatial memory in the water maze was enhanced by ingestion of (–)epicatechin, especially in combination with exercise. Improved spatial memory was associated with increased angiogenesis and neuronal spine density, but not newborn cell survival, in the dentate gyrus of the hippocampus. Moreover, microarray analysis showed upregulation of genes associated with learning and downregulation of markers of neurodegeneration in the hippocampus. Together, our data show that ingestion of a single flavanol improves spatial memory retention in adult mammals.

Key words: flavanols; (–)epicatechin; learning and memory; Morris water maze; angiogenesis; spines

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Received Feb. 28, 2007; revised April 24, 2007; accepted April 24, 2007.

Correspondence should be addressed to Dr. Fred H. Gage, Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037. Email: gage{at}salk.edu

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