2007 Annual Report 1a.Objectives (from AD-416) Phase 1 - In previous studies we determined the effects of purple grape juice PGJ supplementation on behavioral aging using paradigms sensitive to: motor (probes sensitive to balance, strength, coordination) and cognitive (short- and long-term memories) behaviors. (Aim 1). Since it may be that any observed PGJ reductions in motor and cognitive behavioral deficits may involve increases in anti-oxidant and anti-inflammatory protection, and that since we believe that high antioxidant and putative high anti-inflammatory activity of PGJ may be responsible for these positive benefits, we began to determine whether this may be reflected in increased antioxidant or anti-inflammatory activity both peripherally and centrally (Aim 2). The present experiment will be carried as a follow-up to our previous work to assess the role of proanthocyanidins and anthocyanins on motor deficits in aged rodents. By comparing three juices which contain varying amounts of proanthcyandins and anthocyanins, it will allow us to determine the relative contribution of the polyphenols in the different grape juices to the behavioral effects that we have observed previously. Phase 2 - Experiments will be carried out to assess the role of proanthocyanidins and anthocyanins in these beneficial effects by comparing 30% concentrations of three juices: a) concord grape juice which contains both proanthocyanindins and anthocyanins, b) Niagra, which contains proanthocyanidins but no anthocyanins and Thompsons, which contains neither of these polyphenolic classes. 1b.Approach (from AD-416) In our previous study the effects of purple grape juice (PGJ) supplementation on age-sensitive motor and cognitive behaviors was assessed aged rats (Aim 2). We determined the motor performance on: rod and plank waling, wire suspension, inclined screen, and accelerating rotarod performance. Cognitive function was examined using Morris water maze. All of these tests have been validated previously as being age sensitive (e.g. demonstrated a significant decline as a function of age). We also set up procedures to examine serum antioxidants and anti-inflammatories not only by examining some central markers (e.g., Il-1 beta, OX-6) but also by determining the protective effects of the serum against oxidative and inflammatory stressors in our cell models. In addition, the native protection of various tissues in the PGJ-supplemented animals against oxidative or inflammatory insult will be examined in vitro preparations. In the present study we will compare 30% concentrations given to 19 month old animals for six weeks of the following: a) concord grape juice which contains both proanthocyanindins and anthocyanins, b) Niagara, which contains proanthocyanidins but no anthocyanins and Thompsons, which contains neither of these polyphenolic classes. The supplemented animals will be tested on the several motor tests administered once separated by a break between tasks: Rats will be tested in a random manner, with the restriction that one rat from each juice group be tested in succession. The tests will also include: Rod walking, Wire suspension, Plank walking, Inclined screen, and Accelerating rotarod, which measures fine motor coordination, balance, and resistance to fatigue by assessing the duration that a rat can remain standing/walking on a rotating, slowly accelerating rod. Phase 2 - Forty-five male 19 month old animals will be individually housed, provided food and water ad libitum and maintained on a 12 hour light/dark cycle. Following an acclimatization period, the animals will be weight-matched and then randomly assigned to one of three juice groups- Concord, Niagra or Thompson’s grape juice. They will be given 50% concentrations of the respective juices provided by Welch Foods. The group of animals will be given one of these drinks for eight weeks before motor testing. Weights will be recorded during this period and during behavioral testing. A food intake and juice intakes will also be performed during the course of the study. A battery of age-sensitive tests of psychomotor behavior will be administered in a randomized order to the animals at the end of the sixth week following grape juice treatment. Each test will be performed once, separated by a break between tasks. Animals will be tested in a random manner, with the restriction that one animal from each juice group be tested in succession. Briefly, the tests will include:. 1)Rod walking,. 2)Wire suspension, . 3)Plank walking, which measures balance and coordination by exposing the animals to three different sizes of horizontal planks;. 4)Inclined screen, and. 5)Accelerating rotarod. At the conclusion of the experiment we will assess dopamine release. 3.Progress Report This report serves to document research conducted under a Trust Fund Cooperative Agreement between ARS and Welch’s Foods. Animals and humans show increased motor and cognitive declines with aging, which are thought to be due to increased susceptibility to the long-term effects of oxidative stress and inflammation. Previous findings have suggested that improvements in these age-related declines might be accomplished by increasing the dietary intake of polyphenolics found in fruits and vegetables, especially those identified as being high in antioxidant and anti-inflammatory activity. Therefore, we investigated the beneficial effects of two concentrations (10% and 50%) of Welch's Concord grape juice compared to a calorically-matched placebo for their effectiveness in reversing age-related deficits in behavioral and neuronal function in aged Fisher 344 rats. Rats that drank the 10% grape juice from age 19 to 21 months had improvements in oxotremorine-enhancement of K+-evoked release of dopamine from striatal slices as well as cognitive performance on the Morris water maze, while the 50% grape juice produced improvements in motor function. These findings suggest that, in addition to their known beneficial effects on cancer and heart disease, polyphenolics present in foods may be beneficial in reversing the course of neuronal and behavioral aging, possibly through a multiplicity of direct and indirect effects that can affect a variety of neuronal parameters. The manuscript written from this study has been published, and was cited in a previous report. We continued these studies by assessing grape juices of varying anthocyanin or proanthocyanin levels on these behaviors in aged animals. The behavioral assays have been carried out, as well as assessments of dopamine release, and we are now analyzing the results and will write the manuscript. This project is now terminated. Additional details of this research can be found in the report for the parent CRIS 1950-51000-063-00D Nutritional Modulation of Brain Aging and Cognitive Decline.