Muthaiyah B., M.M. Essa, V. Chauhan, A. Chauhan, 2011. Protective effects of walnut extract against amyloid beta peptide-Induced cell death and oxidative stress in PC12 cells. Neurochem Res. Jun 25. [Epub ahead of print]
Amyloid beta-protein (Aβ) is the major component of senile plaques and cerebrovascular amyloid deposits in individuals with Alzheimer’s disease. Aβ is known to increase free radical production in neuronal cells, leading to oxidative stress and cell death. Recently, considerable attention has been focused on dietary antioxidants that are able to scavenge reactive oxygen species (ROS), thereby offering protection against oxidative stress. Walnuts are rich in components that have anti-oxidant and anti-inflammatory properties. The inhibition of in vitro fibrillization of synthetic Aβ, and solubilization of preformed fibrillar Aβ by walnut extract was previously reported. The present study was designed to investigate whether walnut extract can protect against Aβ-induced oxidative damage and cytotoxicity. The effect of walnut extract on Aβ-induced cellular damage, ROS generation and apoptosis in PC12 pheochromocytoma cells was studied. Walnut extract reduced Aβ-mediated cell death assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction, and release of lactate dehydrogenase (membrane damage), DNA damage (apoptosis) and generation of ROS in a concentration-dependent manner. These results suggest that walnut extract can counteract Aβ-induced oxidative stress and associated cell death.
Willis, L.M., D.F. Bielinski, D.R. Fisher, N.R. Matthan, J.A. Joseph, 2010. Walnut extract inhibits LPS-induced activation of Bv-2 microglia via internalization of TLR4: possible involvement of phospholipase D2. Inflammation DOI: 10.1007/s10753-010-9189-0.
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 (TNFα) 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.
Willis, L.M., B. Shukitt-Hale, J.A. Joseph, 2009. Modulation of cognition and behavior in aged animals: role for antioxidant- and essential fatty acid–rich plant foods. Am J Clin Nutr. 89 (suppl):1602S–6S.
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.
Willis, L.M., B. Shukitt-Hale, V. Cheng, J.A. Joseph, 2009. Dose-dependent effects of walnuts on motor and cognitive function in aged rats. British Journal of Nutrition. 101:1140–1144.
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 rat
Willis, L.M., B. Shukitt-Hale, J.A. Joseph, 2009. Dietary polyunsaturated fatty acids improve cholinergic transmission in the aged brain. Genes Nutr. 4:309–314.
The cholinergic theory of aging states that dysfunction of cholinergic neurons arising from the basal forebrain and terminating in the cortex and hippocampus may be involved in the cognitive decline that occurs during aging and Alzheimer’s disease. Despite years of research, pharmacological interventions to treat or forestall the development of Alzheimer’s disease have primarily focused on enhancing cholinergic transmission, either through increasing acetylcholine (ACh) synthesis or inhibition of the acetylcholinesterase enzyme responsible for ACh hydrolysis. However, recent studies have indicated that dietary supplementation can impact the cholinergic system, particularly during aging. The purpose of the present review is to examine the relevant research suggesting that cholinergic functioning may be maintained during aging via consuming a diet containing polyunsaturated fatty acids (PUFAs). The data reviewed herein indicate that, at least in animal studies, inclusion of PUFAs in the diet can improve cholinergic transmission in the brain, possibly leading to improvements in cognitive functioning.
Joseph, J.A., B. Shukitt-Hale, L.M. Willis, 2009. Grape juice, berries, and walnuts affect brain aging and behavior. J. Nutr. 139: 1813S–1817S.
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 kB). 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.
