Fruit polyphenols in brain aging: Effects on Signaling, Neurogenesis and Behavior





J.A. Joseph, G. Casadesus, D. Ingram and B. Shukitt-Hale,

JM USDA Human Res. Ctr. on Aging at Tufts University, 711 Washington St., Boston, MA 02111, USA



It is becoming increasing clear that while the research involving the molecular biology of and the determination of the genetic mechanisms of aging involves elegant science associated with state of the art techniques, it is clear that practical information on how to forestall or reverse the deleterious effects of aging may be years away. If this is the case, then it becomes prudent to try to establish other methods that may be utilized today to alter the course of aging. Numerous epidemiological studies have indicated that individuals who consume a diet containing high amounts of fruits and vegetables may prevent age-related disease such as Alzheimer Disease. Research from our laboratory has suggested that dietary supplementation with fruit or vegetable extracts high in antioxidants (e.g., blueberry, BB, spinach) can decrease the enhanced vulnerability to oxidative stress (OS) that occurs in aging and these reductions are expressed as improvements in behavior. Recent examinations using striatal tissue isolated from BB supplemented aged animals have shown that striatal slices show reductions in H2O2 -induced decrements in muscarinic receptor sensitivity. Moreover, there are also indications that BB supplementation can reduce the sensitivity to neurotoxic agents (kainic acid) that induce oxidative stress and inflammation. Additional experiments suggest that BB effects also may include enhancement of neuronal signaling, and that these increases can offset the putative deleterious consequences of amyloid beta deposition on behavior in APP/PS-1 mice. Therefore, it appears that polyphenolic compounds such as those found in BB may exert their beneficial effects by enhancing the endogenous antioxidant and neuronal signaling capabilities of the organism. In addition, recent work from our laboratory has indicated that one of the most striking effects of BB supplementation may involve increases in neurogenesis. The results have indicated that aged BB-supplemented rats, tested in the radial arm water maze (RAWM) and given injections of BrdU, showed a greater number of proliferating cells in the dentate gyrus (p <0.05) than control cells and these numbers were inversely correlated with the number of errors in the RAWM performance [i.e., as the number of proliferated cells increased, the number of memory errors decreased (reference memory errors: r = - 0.654, p< .05, working memory errors: r = -0.646, p< .05, total memory errors: r = -0.587, p=.08). RAWM errors were also inversely correlated with the number of the anthocyanins that were localized in regions such as the cortex in the BB-supplemented animals. Taken together, these findings suggest that antioxidant-rich fruits such as BBs may improve cognitive performance by increasing proliferation of neural precursor cells in the hippocampus and enhancing signaling in areas such as cortex, hippocampus, and striatum which may offset deficits in aging.




Key words: polyphenolics, brain, behavior, signaling, neurogenesis







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