Plant-Derived Flavanol (−)Epicatechin Enhances Angiogenesis and Retention of Spatial Memory in Mice

Abstract

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, (Ϫ)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 (Ϫ)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.

The Flavanol (−)-Epicatechin Prevents Stroke Damage through the Nrf2/HO1 Pathway

“…For example, epidemiologic data have shown that in Kuna Indians, chronic consumption of an ECrich cocoa drink has cardiovascular benefits that result from augmented levels of nitric oxide (Schroeter et al, 2006). In addition, it has been reported that EC consumption enhances cognition and spatial memory by increasing angiogenesis and neuronal spine density in the dentate gyrus of the hippocampus (van Praag et al, 2007). Our current results reveal that HO1 is at least partially required for EC activity.…”

“…Another criterion of STAIR is that the drug must cross the blood-brain barrier. Available evidence indicates that EC does cross the blood-brain barrier (Abd El Mohsen et al, 2002), as epicatechin glucuronide and 3 0 -O-methyl epicatechin glucuronide have been observed in rat brain for up to 10 days after oral administration of EC (van Praag et al, 2007). Furthermore, after transient ischemia, the blood-brain barrier is likely to be more permeable, especially in the surrounding ischemic region.…”

Running enhances spatial pattern separation in mice

“…There was no difference between the groups in percentage of BrdU/NeuN-positive cells [t (18) Vasculature. Previous work has shown that exercise affects dentate gyrus vasculature (10,28). Coronal sections from the adult and aged groups were stained with tomato lectin.…”

Polyphenols and brain health

“…Blueberry appears to have a pronounced effect on short-term (Ramirez et al, 2005) and long-term memory (Casadesus et al, 2004), and animal studies have provided further evidence for the efficacy of blueberries (Williams et al, 2008;Rendeiro et al, 2012), indicating that improvements in spatial memory may emerge within 3 weeks, the equivalent of about 3 years in humans. In addition, pure (À)-epicatechin (500 mg/g) was observed to enhance the retention of spatial memory in C57BL/6 mice (8-10 week old), especially when combined with exercise (van Praag et al, 2007), similarly to green tea catechins (0.025-0.1% w/v) (Li et al, 2009a). The mechanisms seem to involve an indirect action on the dentate gyrus (DG) (Casadesus et al, 2004;Burke and Barnes, 2006;Rendeiro et al, 2012;Rendeiro et al, 2013).…”

“…Furthermore, ageing is known to impair vascularisation, endothelial function and decreases endothelial progenitor cell recruitment, which could adversely affect neurogenesis. Therefore, the influence of dietary agents on angiogenesis (van Praag et al, 2007) and the production of vascular derived factors are also likely to influence neurogenesis (Casadesus et al, 2004). Ultimately, the effects of polyphenols on the hippocampus are likely to be very dependent on local concentration and, at present, it remains unclear whether polyphenols induce global changes in hippocampal (and other brain region) morphology/function, or are capable of inducing changes within specific hippocampal sub-regions.…”