Location: Human Nutrition Research Center on Aging
Project Number: 1950-51000-063-00
Start Date: May 01, 2004
End Date: Mar 19, 2009
LAB:Nutrition and Cognition Collaboration will continue with the Framingham Heart Study cohorts to examine prospective relationships among nutritional status, cognitive performance, homocysteine, and brain morphology by imaging. Using the homebound elderly population, we will study these relationships first cross-sectionally, and then prospectively. We will add other factors, including antioxidant vitamin status and its relation to inflammatory markers and adhesion molecules in the vasculature. We have designed a trial as an adjunct to the large homocysteine lowering intervention on subjects who have undergone renal transplantation to measure the impact of homocysteine lowering on cognitive decline and performance. The animal models we intend to use are the apoE knockout, the APP/PSI and an APP/London, in which we can modify nutritional status with respect to B vitamins and homocysteine levels and examine the relationships between increased sensitivity to behavioral decline. We will compare age-related status of membrane sphingolipids and vitamins K & A in brain regions controlling behavior in aged Fisher rats. We will also compare the status of membrane sphingolipids, one carbon metabolism, and neuronal viability in a human neuronal cell culture model. LAB:Neuroscience COS-7 cells transfected with various muscarinic receptor subtypes and their chimerics will be used to identify the structural and membrane lipid raft differences contributing to increased oxidative stress vulnerability by exposing them to dopamine and assessing alterations in calcium flux and viability. Motor and cognitive assessments will be undertaken in senescent rats given diets supplemented with whole berryfruits or extracts derived from them. Correlative determinations of neurogenesis, neuronal signaling and gene activation or inhibition will also be undertaken in various brain regions of these control and supplemented animals.