2010 Annual Report
2. Characterize mechanisms by which nutritionally induced hyperhomocysteinemia affects neuronal function and cognitive performance using transgenic and other animal models of human cognitive decline.
LAB: Neuroscience 1. Use cell models to develop mechanistic interpretations of the positive benefits of berry polyphenols and fatty acids by examining their direct effects on deficits in stress and protective signaling.
2. Establish the effects of dietary berry fruit extracts and/or fatty acids on behavioral and neuronal deficits in aging to assess the mechanisms involved and the most effective polyphenols/fatty acids in animal and human models.
LAB: Neuroscience The focus of the current project is to elucidate the mechanisms involved in the beneficial effects of berry fruit and polyunsaturated fatty acids (PUFAs) from fish or nut oils on reducing neurodegeneration mediated by oxidative stress (OS) and inflammation (INF). Mixed neuron/ glial cultures obtained from rats of different ages will be employed to delineate the neuroprotective effects of berry fruit or PUFA against OS/INF and subsequent stress mediated by glial cells. Additionally, muscarinic receptor-transfected COS-7 cells will be used to assess OS/INF localization and the effects of membrane lipids on the cellular responses to OS/INF. Extensive motor and cognitive assessments will also be made of senescent animals fed diets containing berry fruit or PUFAs. Finally, we will translate the behavioral findings obtained in our animal studies to the human condition by examining the effects of berry fruit or walnut supplementation on human gait and motor ability. This project will contribute to fundamental new knowledge of the putative role of berry fruit and PUFAs on reducing OS/INF and behavioral deficits in aging. These studies will span basic cellular signaling, animal behavior and cognition, and human motor abilities, allowing for a comprehensive examination of the beneficial effects of berry fruit and nutritional PUFAs on the aging brain.
LAB: Neuroscience We have shown that supplementation with fruits and vegetables can forestall and reverse the deleterious effects of aging on neuronal functioning and behavior. While fruits and vegetables may have direct effects on oxidative stress (OS) and inflammation in aging, polyphenolic compounds may also enhance protective signaling and neuronal growth. Discovery of these additional mechanisms might lead to important dietary information to an aging population. Additionally, determining which components might be responsible for the beneficial effects is also important, although it might be that the combination of polyphenols or fatty acids present in berries or nuts may have synergistic effects which provide increased protection from age-related declines relative to individual constituent compounds. This year we continued to study the mechanisms responsible for the beneficial effects of berry fruit. In one study we showed that three berry extracts (blueberry, strawberry and acai berry) were able to rescue neurons through induction of autophagy, a process by which toxic debris is recycled and cleared in neurons. We also began to determine the effects of the berry fruit on stress signaling from different types of brain cells such as microglia, astrocytes, and neurons derived from the mixed cultures. We showed that blueberries (BB) and strawberries (SB) could protect neurons through auxiliary effects on astrocytes when they were co-cultured with the neurons, as they are in the brain. Additionally, we began to examine individual components from berry fruit, acai berry to determine which polyphenolic families might be responsible for their beneficial effects. In addition, in an animal study, we compared the effects of specific compounds found in BBs with the effect of the whole berry on the mobility and behavior of aged rats in doses equivalent to 2 cups/day in humans. The findings suggested that proanthocyanidins may be the polyphenolic family responsible for the protective effects of blueberries, although the whole berry was also effective. Finally, we began to explore age-related alterations in balance, gait, and cognition in humans in a pilot study to validate the gait apparatus and several cognitive tests. Preliminary results show that the methods are sufficiently robust to detect age-related declines in balance, gait, and cognition. This information will allow us to plan a subsequent study to investigate the ability of blueberry or strawberry supplementation to attenuate these age-related performance declines.
Krikorian, R., Nash, T.A., Shidler, M.D., Shukitt Hale, B., Joseph, J.A. 2009. Concord Grape Juice Supplementation Improves Memory Function In Older Adults with Mild Cognitive Impairment. British Journal of Nutrition. 103:730-734.
Ismayil, A., Spangler, E., Shukitt Hale, B., Joseph, J.A., Ingram, D., Talan, M. 2009. Survival and cardioprotective benefits of long-term blueberry enriched diet in dilated cardiomyopathy following myocardial infarction in rats. PLoS One. 4(11):e7975.
Krikorian, R., Shidler, M., Nash, T., Kalt, W., Vinqvist-Tymchuk, M., Shukitt Hale, B., Joseph, J.A. 2010. Blueberry supplementation improves memory in older adults. Journal of Agricultural and Food Chemistry. 58:3996-4000.
Ahmet, I., Spangler, E., Shukitt Hale, B., Juhaszova, M., Sollott, S.J., Joseph, J.A., Ingram, D.K., Talan, M. 2009. Blueberry-enriched diet protects rat heart from ischemic damage. PLoS One. 4(5934):1-10.
Willis, L., Shukitt Hale, B., Joseph, J.A. 2009. Dietary polyunsaturated fatty acids improve cholinergic transmission in the aged brain. Genes and Nutrition. 4:309-314.
Joseph, J.A., Bielinski, D., Fisher, D.R. 2010. Blueberry antagonism of C-2 ceramide disruption of Ca2+ responses and recovery in MAChR-transfected COS-7 cells involves alterations in stress signaling. Journal of Agricultural Food & Chemistry. 58:3380-3392.
Joseph, J.A., Shukitt Hale, B., Willis, L. 2009. Grape juice, berries and walnuts affect brain aging and behavior. Journal of Nutrition. 139:1813S-1817S.
Joseph, J.A., Shukitt Hale, B., Willis, L. 2009. Fruits, Nuts, and Brain Aging: Nutritional Interventions Targeting Age-Related Neuronal and Behavioral Deficits. In: Packer, L., Sies, H., Eggersdorfer, M., and Cadenas, E., editors. Micronutrients and Brain Health. Boca Raton, FL: CRC Press. p. 179-188.
Joseph, J.A., Cole, G., Head, E., Ingram, D. 2009. Nutrition, brain aging, and neurodegeneration. Journal of Neuroscience. 29:12795-12801.
Willis, L., Bielinski, D.F., Fisher, D.R., Matthan, N.R., Joseph, J.A. 2010. Walnut extract inhibits LPS-induced activation of BV-2 microglia via internalization of TLR4: possible involvement of phospholipase D2. Inflammation. 33(5):325.
Joseph, J.A., Shukitt Hale, B., Brewer, G.J., Weikel, K.A., Kalt, W., Fisher, D.R. 2010. Differential protection among fractionated blueberry polyphenolic families against DA-, ABeta 42 and LPS-induced decrements in Ca2+ buffering in primary hippocampal cells. Journal of Agriculture and Food Chemistry. 58:8196-8204.