Location: Boston, Massachusetts
Project Number: 8050-51000-081-05-T
Project Type: Trust Fund Cooperative Agreement
Start Date: Aug 15, 2011
End Date: Aug 31, 2014
A major focus of this proposal is concerned with the possible beneficial effects of dietary supplementation of antioxidants and anti-inflammatories in reducing the deleterious effects of reactive oxygen species and inflammation when their levels overwhelm the organism’s defense capacities and damage to cellular macromolecules such as lipids, proteins, and DNA occurs. There have been numerous studies in which antioxidants have been examined with respect to reducing the deleterious effects of brain aging, with mixed results. However, our research suggests that the combinations of antioxidant/anti-inflammatory polyphenolics found in fruits and vegetables may show efficacy in aging. Therefore, in the present study we will determine the effects of these supplementations on stress signaling, microglial activation and neurogenesis and correlate these with alterations in behavioral parameters. The effects of these supplementations on neurogenesis and differentiation will be examined using immunocytochemistry, bromodeoxyuridine (BrDU) incorporation in hippocampus obtained from the supplemented behaviorally-assessed animals.
We will utilize several techniques (e.g., Western blot analyses and immunocytochemistry) to assess the changes in several markers of phosphorylation that are important in cell communication (e.g., calcium-dependent protein kinase C, PKC; extracellular signal regulated kinases, ERK) and other markers of stress signaling (e.g., p38 MAPK) in vitro in BV-2 cells and in primary hippocampal neurons.