Damaging Effects of a Saturated Fat/Cholesterol Diet toe the Brain

描述(由申请人提供)：本文包含的研究计划概述了一项研究计划，以调查饱和脂肪和高胆固醇饮食(SFC)对学习和记忆行为以及海马体形态的影响。随着婴儿潮一代的老龄化和现代进步使我国人口的平均寿命更长，与年龄相关的疾病的数量正在增加。这项研究的重点是与年龄相关的认知能力下降，特别是白介素1(IL-1)的作用，这是一种已知存在于海马体的细胞因子。虽然有许多可能导致认知下降的因素，但这项研究重点关注并探索了饮食脂肪的作用，特别是对海马体形态的作用。之所以选择海马体，是因为它是一个明确定义的学习和记忆过程的地点，并且已经被证明在与认知能力下降相关的疾病中表现出巨大的神经元损失，如阿尔茨海默病。提出了行为实验、形态实验和生化实验。我们实验室以前的工作已经表明，饱和脂肪和高胆固醇饮食对12天的水放射状手臂迷宫的表现有不利影响。另一项研究显示，在各种饮食包括饱和脂肪饮食和高胆固醇饮食后，树突完整性、激活的小胶质细胞数量和血管结构发生了变化。这两项研究都只包括八周的饮食治疗。这里包含的研究建议旨在通过利用长期模型(6个月)以及测试潜在的机制：海马体中IL-1的增加来推进这些研究。根据审查员的评论，这份修订后的提案更有针对性。第一个目标是评估海马区和外周的IL-1水平，一些行为测量，以及海马区的形态，并比较年轻和老年动物的结果。我们假设，与年轻动物相比，老年动物的所有影响都更差，特别是那些接受SFC饮食治疗的动物。目的2进一步验证IL-1在饮食诱导的认知损伤中的作用。我们推测IL-1ra对SFC饮食对老龄动物的保护作用。提议的目标将为我提供行为技术、行为统计分析和细胞因子测量方面的培训。随着肥胖症在美国的上升和流行比例以及与年龄相关的疾病的增加，这项研究对公共健康具有明确而重要的影响。“西方饮食”已被证明对心血管健康有害；在这里，我们调查它在与年龄相关的认知衰退中的作用。

DESCRIPTION (provided by applicant): 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.