The research proposal contained herein outlines a program of study to Investigate the effects of a saturated fat and high cholesterol diet (SFC) on learning and memory behavior and hippocampal morphology. As the baby boomer generation ages and modern-day advances allow our country's population to live a longer average lifespan, the number of age-associated disorders are increasing in prevalence. This study focuses on age-associated cognitive decline, and specifically the role of interleukin 1 (IL-1), a cytokine known to be present in the hippocampus. While there are many possible contributors to cognitive decline, this study focuses on and explores the role of dietary fats, particularly on hippocampal morphology. The hippocampus was chosen, as it is a clearly defined site for learning and memory processes, and has been shown to exhibit great neuronal loss in diseases related to cognitive decline such as Alzheimer's disease. Behavioral, morphological and biochemical experiments are proposed. Previous work in our laboratory has shown detrimental effects of a saturated fat and high cholesterol diet on performance in the 12-day water radial arm maze. Another study revealed alterations to dendritic integrity, number of activated microglia, and blood vessel structure following various diets including a saturated fat diet and a high cholesterol diet. Both of these studies included diet treatment for just eight weeks. The research proposal contained herein is designed to advance these studies by utilizing a long-term model (6 months) as well as testing a potential mechanism: increased IL-1 in the hippocampus. This revised proposal is more focused according to the reviewer's comments.
The first aim will evaluate IL-1 levels in the hippocampus and periphery, a number of behavioral measures, and hippocampal morphology and compare results between young and aged animals. We hypothesize all effects to be worse in aged animals compared to young, especially those treated with the SFC diet.
Aim 2 will further test the role of IL-1 in diet induced cognitive damage. We hypothesize the IL- 1 Ra will rescue effects of the SFC diet in the aged animals. The proposed aims will provide me with training in behavioral techniques, statistical analysis of behavior, and cytokine measurements. This study has a clear and important implication for public health with the rise and epidemic proportion of obesity in the United States and the rise in age-related disorders. The """"""""Western diet"""""""" has been shown to be detrimental to cardiovascular health;here we investigate its role in age-related cognitive decline.
| Freeman, Linnea R; Haley-Zitlin, Vivian; Rosenberger, Dorothea S et al. (2014) Damaging effects of a high-fat diet to the brain and cognition: a review of proposed mechanisms. Nutr Neurosci 17:241-51 |
| Freeman, Linnea R; Granholm, Ann-Charlotte E (2012) Vascular changes in rat hippocampus following a high saturated fat and cholesterol diet. J Cereb Blood Flow Metab 32:643-53 |
| Freeman, Linnea R; Haley-Zitlin, Vivian; Stevens, Cheryl et al. (2011) Diet-induced effects on neuronal and glial elements in the middle-aged rat hippocampus. Nutr Neurosci 14:32-44 |
