The beneficial effects of berries on cognition, motor behaviour and neuronal function in ageing.

Previously, it has been shown that strawberry (SB) or blueberry (BB) supplementations, when fed to rats from 19 to 21 months of age, reverse age-related decrements in motor and cognitive performance. We have postulated that these effects may be the result of a number of positive benefits of the berry polyphenols, including decreased stress signalling, increased neurogenesis, and increased signals involved in learning and memory. Thus, the present study was carried out to examine these mechanisms in aged animals by administering a control, 2 % SB- or 2 % BB-supplemented diet to aged Fischer 344 rats for 8 weeks to ascertain their effectiveness in reversing age-related deficits in behavioural and neuronal function. The results showed that rats consuming the berry diets exhibited enhanced motor performance and improved cognition, specifically working memory. In addition, the rats supplemented with BB and SB diets showed increased hippocampal neurogenesis and expression of insulin-like growth factor 1, although the improvements in working memory performance could not solely be explained by these increases. The diverse polyphenolics in these berry fruits may have additional mechanisms of action that could account for their relative differences in efficacy.

Angiotensin receptor blockers and angiogenesis: clinical and experimental evidence.

Angiotensin II type 1 receptor antagonists [ARBs (angiotensin receptor blockers)] are indicated for BP (blood pressure)-lowering, renal protection and cardioprotection in patients unable to tolerate ACEIs (angiotensin-converting enzyme inhibitors). A recent meta-analysis revealed an association between ARBs and tumour development, possibly due to enhancement of angiogenesis. However, published evidence is conflicting on the effects of ARBs on angiogenesis or the expansion of the existing vascular network. ARBs have been shown to exert primarily anti-angiogenic effects in basic science studies of cancer, retinopathy, peripheral artery disease and some models of cardiovascular disease. In animal and cellular models of myocardial infarction and stroke, however, ARB administration has been associated with robust increases in vascular density and improved recovery. The aim of the present review is to examine the angiogenic effects of ARBs in animal and cellular models of relevant disease states, including proposed molecular mechanisms of action of ARBs and the clinical consequences of ARB use.

Walnut extract inhibits LPS-induced activation of BV-2 microglia via internalization of TLR4: possible involvement of phospholipase D2.

Walnuts are a rich source of essential fatty acids, including the polyunsaturated fatty acids alpha-linolenic acid and linoleic acid. Essential fatty acids have been shown to modulate a number of cellular processes in the brain, including the activation state of microglia. Microglial activation can result in the generation of cytotoxic intermediates and is associated with a variety of age-related and neurodegenerative conditions. In vitro, microglial activation can be induced with the bacterial cell wall component lipopolysaccharide (LPS). In the present study, we generated a methanolic extract of English walnuts (Juglans regia) and examined the effects of walnut extract exposure on LPS-induced activation in BV-2 microglial cells. When cells were treated with walnut extract prior to LPS stimulation, production of nitric oxide and expression of inducible nitric oxide synthase were attenuated. Walnut extract also induced a decrease in tumor necrosis-alpha (TNFalpha) production. We further found that walnut extract induced internalization of the LPS receptor, toll-like receptor 4, and that the anti-inflammatory effects of walnut were dependent on functional activation of phospholipase D2. These studies represent the first to describe the anti-inflammatory effects of walnuts in microglia, which could lead to nutritional interventions in the prevention and treatment of neurodegeneration.

Blueberry supplementation attenuates microglial activation in hippocampal intraocular grafts to aged hosts.

Transplantation of central nervous tissue has been proposed as a therapeutic intervention for age-related neurodegenerative diseases and stroke. However, survival of embryonic neuronal cells is hampered by detrimental factors in the aged host brain such as circulating inflammatory cytokines and oxidative stress. We have previously found that supplementation with 2% blueberry in the diet increases graft growth and neuronal survival in intraocular hippocampal grafts to aged hosts. In the present study we explored possible biochemical mechanisms for this increased survival, and we here report decreased microglial activation and astrogliosis in intraocular hippocampal grafts to middle-aged hosts fed a 2% blueberry diet. Markers for astrocytes and for activated microglial cells were both decreased long-term after grafting to blueberry-treated hosts compared with age-matched rats on a control diet. Similar findings were obtained in the host brain, with a reduction in OX-6 immunoreactive microglial cells in the hippocampus of those recipients treated with blueberry. In addition, immunoreactivity for the pro-inflammatory cytokine IL-6 was found to be significantly attenuated in intraocular grafts by the 2% blueberry diet. These studies demonstrate direct effects of blueberry upon microglial activation both during isolated conditions and in the aged host brain and suggest that this nutraceutical can attenuate age-induced inflammation.

Grape juice, berries, and walnuts affect brain aging and behavior.

Numerous studies have indicated that individuals consuming a diet containing high amounts of fruits and vegetables exhibit fewer age-related diseases such as Alzheimer's disease. Research from our laboratory has suggested that dietary supplementation with fruit or vegetable extracts high in antioxidants (e.g. blueberries, strawberries, walnuts, and Concord grape juice) can decrease the enhanced vulnerability to oxidative stress that occurs in aging and these reductions are expressed as improvements in behavior. Additional mechanisms involved in the beneficial effects of fruits and vegetables include enhancement of neuronal communication via increases in neuronal signaling and decreases in stress signals induced by oxidative/inflammatory stressors (e.g. nuclear factor kappaB). Moreover, collaborative findings indicate that blueberry or Concord grape juice supplementation in humans with mild cognitive impairment increased verbal memory performance, thus translating our animal findings to humans. Taken together, these results suggest that a greater intake of high-antioxidant foods such as berries, Concord grapes, and walnuts may increase "health span" and enhance cognitive and motor function in aging.

Modulation of cognition and behavior in aged animals: role for antioxidant- and essential fatty acid-rich plant foods.

Aging results in the development of cognitive and motor deficits in humans and animals that are evident by midlife. These deficits are thought to stem from neuronal damage and dysfunction as a result of a variety of stressors, including increased oxidative stress and modifications in brain lipid composition. Recent clinical and animal studies have identified nutritional intervention as a viable method to curtail the cognitive aging process. Human studies have been primarily observational and have indicated that inclusion of antioxidant-rich foods in the diet can slow the progression of cognitive decline. Basic science studies investigating nutritional modulation of age-related cognitive decline have focused on foods rich in antioxidants or essential fatty acids. The purpose of this review is to discuss recent advancements in animal research showing that age-related cognitive and behavioral decline can be ameliorated with nutritional supplementation with polyphenol- or polyunsaturated fatty acid-rich plant foods.

Dose-dependent effects of walnuts on motor and cognitive function in aged rats.

Aged rats show decrements in performance on motor and cognitive tasks that require the use of spatial learning and memory. Previously we have shown that these deficits can be reversed by the polyphenolics in fruits and vegetables. Walnuts, which contain the n-3 fatty acids a-linolenic acid and linoleic acid, are a dietary source of polyphenols, antioxidants and lipids. Thus, the present study examined the effects of walnut supplementation on motor and cognitive ability in aged rats. Fischer 344 rats, aged 19 months, were fed a control, or a 2, 6 or 9% walnut diet for 8 weeks before motor and cognitive testing. Results for the motor testing showed that the 2% walnut diet improved performance on rod walking, while the 6% walnut diet improved performance on the medium plank walk; the higher dose of the 9% walnut diet did not improve psychomotor performance and on the large plank actually impaired performance. All of the walnut diets improved working memory in the Morris water maze, although the 9% diet showed impaired reference memory. These findings show for the first time that moderate dietary walnut supplementation can improve cognitive and motor performance in aged rats.

Recent advances in berry supplementation and age-related cognitive decline.

PURPOSE OF REVIEW: To summarize recent findings and current concepts in the beneficial effects of berry consumption on brain function during aging. RECENT FINDINGS: Berryfruit supplementation has continued to demonstrate efficacy in reversing age-related cognitive decline in animal studies. In terms of the mechanisms behind the effects of berries on the central nervous system, recent studies have demonstrated the bioavailability of berry polyphenols in several animal models. These studies have revealed that flavonoids and polyphenols from berries do accumulate in the brain following long-term consumption. Finally, several compelling studies have revealed that berries can influence cell-signaling cascades both in vivo and in cell culture systems. These studies underscore the developing theory that berries and antioxidant-rich foods may be acting as more than just oxygen radical neutralizers in the aging central nervous system. SUMMARY: Antioxidant-rich berries consumed in the diet can positively impact learning and memory in the aged animal. This effect on cognition is thought to be due to the direct interaction of berry polyphenols with aging neurons, reducing the impact of stress-related cellular signals and increasing the capacity of neurons to maintain proper functioning during aging.

Dietary blueberry supplementation affects growth but not vascularization of neural transplants.

Transplantation of neural tissue has been attempted as a treatment method for neurodegenerative disorders. Grafted neurons survive to a lesser extent into middle-aged or aged hosts, and survival rates of <10% of grafted neurons is common. Antioxidant diets, such as blueberry, can exert powerful effects on developing neurons and blood vessels in vitro, but studies are lacking that examine the effects of these diets on transplanted tissues. In this study, we examined the effects of a blueberry diet on survival, growth, and vascularization of fetal hippocampal tissue to the anterior chamber of the eye of young or middle-aged female rats. Previous work from our group showed significant increase in neuronal survival and development with blueberry diet in grafts. However, the effects of antioxidant diet on vascular development in grafts have not been explored previously. The age of the host affected individual vessel morphology in that aged hosts contained grafts with thick, undeveloped walls, and wider lumen. The blood-brain barrier also appeared to be affected by the age of the host. The blueberry diet did not affect vessel morphology or density of vessel-associated protein markers but gave rise to significantly increased growth capacity, cytoarchitecture, and the final size of hippocampal grafts.