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Fruit and Vegetable Supplementation

in the Aging Brain:

"Priming" the Brain Against the Ravages of Time

E-Newsletter No. 63

Abstract of a presentation given at the Sixth Annual Dementia Congress General Session on Nov. 3, 2007 by James A. Joseph, PhD

Numerous epidemiological studies have indicated that consumption of a diet containing high amounts of fruits and vegetables may prevent age-related diseases, such as Alzheimer's disease (AD).  A recent report has indicated that individuals who consumed a diet containing 2.5 servings of fruits and vegetables/day were 40% less likely to develop AD.  Reserch from our laboratory has suggested that dietary supplementation with fruit, nut, or vegetable extracts high in antioxidants, (eg, blueberry [BB], blackberry, cranberry, concord grape juice, strawberry [SB], walnuts) can decrease the enhanced vulnerability to oxidative stress (OS) that occurs in aging, and these reductions are expressed in part as improvements in motor and cognitive behavior.  In addition to their antioxidant and anti-inflammatory activities, multiple mechanisms may be involved in the beneficial effects observed by these supplements.  These mechanisms include: a) enhancement of neuronal communication; b) signaling associated with learning and memory; c) neurogenesis; d) reductions in stress signaling.  For example, previous work shows that BB supplementation from 4 to 12 months of age in APP/PS1 mice can offset the putative deleterious effects of amyloid beta deposition on behavior in these mice by increasing extracellular signal-regulated kinase (ERK) and protein kinase C (PKC), 2 important signaling factors in learning and memory.  It also appears that polyphenolic compounds such as those found in BB, may exert beneficial effects by reducing signals produced by oxidative stress and inflammation and enhancing protective signals in the organism.  These protective signals include ERK and insulin growth factor-1 (IGF-1) that promote increases in neurogenesis.  BB can increase ERK, IGF-1, and neurogenesis, and thus far we have found that SB can also induce neurogenesis.  Taken together, these findings, along with those showing increases in ERK and IGF-1 signaling associated with enhancements in cognitive function in the BB-supplemented animals, suggest that antioxidant-rich fruits such as berries and walnuts may improve behavior by enhancing neuronal signaling, and ultimately, neuronal communication.

Like the berries, walnuts contain polyphenols, but in addition, also contain fatty acids that have been shown to have cardiovascular benefits.  As mentioned above, an addtional property of the berry-derived polyphenols may involve reducing stress signaling.  Research using VB-2 mouse microglial cells has indicated that the antioxidant properties of BB and possibly other berryfruits (SB), may be derived at least in part from their ability to inhibit the signals (eg, nuclear factor kappa B [NFxB] and cyclic AMP response element binding protein [CREB], and cytokines) induced by oxidative/inflammatory stressors.  This is an important consideration because overactivation of microglial cells in AD and Parkinson's disease have been shown to be involved in cell loss.  Similar decreases in stress signaling have also been found in BB-created primary hippocampal cells that were exposed to oxidative or inflammatory stressors.  However, in addition we found that the protective signals (eg, mitogen activated protein kinease [MAPK]) were also activated.  The hippocampus is an important memory control area that is affected in AD.  Thus, in addition to the well-known free-radical scavenging effects that are seen with assessments of oxygen radical absorbance capacity (ORAC), it appears that BB, and possibly other fruits and nuts (eg, SB, concord grapes, walnuts), can directly reduce stress signaling and enhance protective signals.  However, the direct antioxidant/anti-inflammatory effects of the berryfruit polyphenols may only represent a small aspect of their beneficial properties in aging.  We believe that this information can be utilized to show that the addition of colorful fruits, such as berryfruits, and nuts, such as walnuts, to the diet can possibly increase "health span" in aging, and provide a "longevity dividend" or economic benefit for slowing the aging process by reducing the incidence and/or delaying the onset of debilitating neurodegenerative disease.

Recommended readings:
Joseph JA, Shukitt-Hale B, Casadesus G.  Reversing the deleterious effects of aging or neuronal communicaiton and behavior the beneficial properties of fruit polyphenolics.  Am J Cln Nutrition, 2005:81(suppl):313S-316S.

Joseph JA, Fisher DR, Bielinski D.  Blueberry extract alters oxidative stress-mediated signaling in COS-7 cells transfected with selectively vulnerable muscarinic receptor subtypes.  J Alz Dxs.  2005:9:35-42.

Joseph JA, Shukitt-Hale B, Lau FC.  Fruit polyphenols and their effects on neuronal signaling and behavior in senescence.  Ann NY Acad Sci.  2007:1100:470-486

Lau FC, Bielinski D, Joseph JA.  Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide-activated VB2 microglia.  J Neurosci Res.  2007:85(5):1010-1017.

Shukitt-Hale B, Carey A, Jenkins D, Rabin B, Joseph JA.  Beneficial effects of fruit extracts on neuronal funciton and behavior in a rodent model of accelerated aging.  Neurobiol Aging, 2007:28:1187-1194.

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