Cholesterol and Copper Affect Learning and Memory
胆固醇和铜影响学习和记忆
基本信息
- 批准号:9085605
- 负责人:
- 金额:$ 13.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-07-01 至 2016-05-31
- 项目状态:已结题
- 来源:
- 关键词:Action PotentialsAffectAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAmino Acid SequenceAmyloid beta-ProteinAmyloid beta-Protein PrecursorAnemiaAnimal Disease ModelsAnimal ModelAnimalsAntidotesAtherosclerosisBehaviorBehavioralBehavioral ModelBile Acid Biosynthesis PathwayBiochemicalBloodBrainCardiovascular DiseasesCardiovascular systemCellsCellular StructuresCholesterolCopperCoronary heart diseaseDataDepositionDietDietary CholesterolEndocrineExtinction (Psychology)FailureGoalsGrowthHealthHeart DiseasesHeart RateHippocampus (Brain)HormonesHumanInflammatoryLeadLearningLinkMeasuresMedialMediatingMembraneMemoryMemory impairmentMental RetardationMetabolismMindModelingModificationMolecularNatureNictitating MembraneOryctolagus cuniculusPathogenesisPatientsPeripheralPlayPrefrontal CortexProductionProgress ReportsPropertyProsencephalonPyramidal CellsResearchRisk FactorsRoleSenile PlaquesSeriesSignal TransductionSliceStructureStudy SectionStudy modelsSynaptic MembranesSynaptic plasticityTechniquesTestingTimeToxic effectTrace metalWidespread DiseaseWorkWritingabeta accumulationbaseclassical conditioningconditioningcytokineexpectationextracellularfeedinginnovationinterestlong term memorymemory acquisitionmemory recallmemory retentionneural modelneuronal excitabilitynutritionpatch clamppreventpulmonary functionrelating to nervous systemrepairedresearch studyresponsetool
项目摘要
DESCRIPTION (provided by applicant): Cholesterol and copper are crucial to nutrition and normal brain function but recent evidence also implicates both in Alzheimer's disease. Cholesterol is important for cell structure, repair and signaling, hormone production and bile acid synthesis but is also a major risk factor for atherosclerosis, coronary heart disease, and Alzheimer's disease. A high-cholesterol diet can result in beta amyloid deposits - a hallmark of Alzheimer's disease. Copper is important for growth, cardiovascular, endocrine and pulmonary function but copper imbalance has been linked to mental retardation, anemia, toxicosis and Alzheimer's disease. Copper is involved in beta amyloid metabolism, aggregation, toxicity, appears to be elevated in the blood of Alzheimer's patients, and is one of the trace metals found in senile plaques of post-mortem Alzheimer's brains. We have established that cholesterol and copper affect classical conditioning of the rabbit nictitating membrane response and heart rate. New data suggest cholesterol can retard the recall of "old" memories - those formed before a high cholesterol diet. The hypothesis on which the current renewal is based is that cholesterol and beta amyloid affect learning and memory and that the mechanism involved is mediated by direct and indirect effects of cholesterol on the CNS. The current proposal tests this hypothesis with three specific aims will focus on cellular and molecular mechanisms underlying cholesterol effects on acquisition of new memories (Specific Aim 1) and investigate the effects of cholesterol on memory retention (Specific Aim 2). Once we understand the effects of cholesterol on retention we will then examine its cellular and molecular mechanisms (Specific Aim 3). This work is important because of the impact it will have on understanding the role of dietary cholesterol and beta amyloid deposits in learning and memory and on our understanding of the pathogenesis of failures in learning and memory. The research will be of considerable significance because it will establish a clear role for cholesterol, copper and beta amyloid in learning and memory and advance the field by adding the cholesterol-fed rabbit as a valuable non-transgenic tool to the search for treatments of and a cure for Alzheimer's disease. The proposed work is innovative because it combines classical conditioning of the rabbit NMR - a well- understood behavioral and neural model of learning and memory - with the simple dietary manipulation of feeding cholesterol to examine the effects of cholesterol and beta amyloid - two of the "smoking guns" of Alzheimer's disease.
描述(由申请人提供):胆固醇和铜对于营养和正常大脑功能至关重要,但最近的证据也表明这两种物质都与阿尔茨海默病有关。胆固醇对于细胞结构、修复和信号传导、激素产生和胆汁酸合成很重要,但也是动脉粥样硬化、冠心病和阿尔茨海默病的主要危险因素。高胆固醇饮食会导致β淀粉样蛋白沉积——阿尔茨海默病的一个标志。铜对于生长、心血管、内分泌和肺功能很重要,但铜失衡与智力低下、贫血、中毒和阿尔茨海默病有关。铜参与β淀粉样蛋白的代谢、聚集和毒性,在阿尔茨海默病患者的血液中似乎升高,并且是在死后阿尔茨海默病大脑的老年斑中发现的微量金属之一。我们已经确定胆固醇和铜影响兔子瞬膜反应和心率的经典调节。新数据表明,胆固醇会阻碍“旧”记忆的回忆——那些在高胆固醇饮食之前形成的记忆。当前更新所依据的假设是胆固醇和β淀粉样蛋白影响学习和记忆,并且所涉及的机制是由胆固醇对中枢神经系统的直接和间接影响介导的。目前的提案通过三个具体目标测试这一假设,将重点关注胆固醇对新记忆获取影响的细胞和分子机制(具体目标 1),并研究胆固醇对记忆保留的影响(具体目标 2)。一旦我们了解了胆固醇对保留的影响,我们就会检查其细胞和分子机制(具体目标 3)。这项工作很重要,因为它将对了解膳食胆固醇和β淀粉样蛋白沉积物在学习和记忆中的作用以及我们对学习和记忆失败的发病机制的理解产生影响。这项研究将具有相当重要的意义,因为它将确定胆固醇、铜和β淀粉样蛋白在学习和记忆中的明确作用,并通过将胆固醇喂养的兔子作为一种有价值的非转基因工具来寻找治疗和记忆的方法,从而推动该领域的发展。治疗阿尔茨海默病。拟议的工作具有创新性,因为它结合了兔子核磁共振(一种众所周知的学习和记忆的行为和神经模型)的经典调节与喂养胆固醇的简单饮食操作,以检查胆固醇和β淀粉样蛋白(其中两种“”)的影响。阿尔茨海默病的铁证”。
项目成果
期刊论文数量(17)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Classical conditioning of the rabbit's nictitating membrane response is a function of the duration of dietary cholesterol.
兔子瞬膜反应的经典调节是饮食胆固醇持续时间的函数。
- DOI:
- 发表时间:2007-06
- 期刊:
- 影响因子:3.6
- 作者:Schreurs, Bernard G;Smith;Darwish, Deya S;Stankovic, Goran;Sparks, D Larry
- 通讯作者:Sparks, D Larry
Dietary cholesterol increases ventricular volume and narrows cerebrovascular diameter in a rabbit model of Alzheimer's disease.
在阿尔茨海默氏病兔模型中,膳食胆固醇会增加心室体积并缩小脑血管直径。
- DOI:
- 发表时间:2013-12-19
- 期刊:
- 影响因子:3.3
- 作者:Schreurs, B G;Smith;Lemieux, S K
- 通讯作者:Lemieux, S K
Dietary cholesterol impairs memory and memory increases brain cholesterol and sulfatide levels.
膳食胆固醇会损害记忆力,而记忆力会增加大脑胆固醇和脑硫脂水平。
- DOI:10.1037/a0018253
- 发表时间:2010-02
- 期刊:
- 影响因子:1.9
- 作者:Darwish, Deya S.;Wang, Desheng;Konat, Gregory W.;Schreurs, Bernard G.
- 通讯作者:Schreurs, Bernard G.
Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity.
老年人和阿尔茨海默病大脑中的小胶质细胞营养不良与铁蛋白免疫反应性有关。
- DOI:
- 发表时间:2008-08-01
- 期刊:
- 影响因子:6.2
- 作者:Lopes, Kryslaine O;Sparks, D Larry;Streit, Wolfgang J
- 通讯作者:Streit, Wolfgang J
Cholesterol and copper affect learning and memory in the rabbit.
胆固醇和铜影响兔子的学习和记忆。
- DOI:
- 发表时间:2013
- 期刊:
- 影响因子:0
- 作者:Schreurs; Bernard G
- 通讯作者:Bernard G
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BERNARD G. SCHREURS其他文献
BERNARD G. SCHREURS的其他文献
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{{ truncateString('BERNARD G. SCHREURS', 18)}}的其他基金
Dietary manipulations in rabbits induce the cellular, neuropathological, and cognitive hallmarks of late-onset Alzheimer's Disease
兔子的饮食控制会诱发迟发性阿尔茨海默病的细胞、神经病理和认知特征
- 批准号:
10668423 - 财政年份:2021
- 资助金额:
$ 13.88万 - 项目类别:
Dietary manipulations in rabbits induce the cellular, neuropathological, and cognitive hallmarks of late-onset Alzheimer's Disease
兔子的饮食控制会诱发迟发性阿尔茨海默病的细胞、神经病理和认知特征
- 批准号:
10468188 - 财政年份:2021
- 资助金额:
$ 13.88万 - 项目类别:
Dietary manipulations in rabbits induce the cellular, neuropathological, and cognitive hallmarks of late-onset Alzheimer's Disease
兔子的饮食控制会诱发迟发性阿尔茨海默病的细胞、神经病理和认知特征
- 批准号:
10269381 - 财政年份:2021
- 资助金额:
$ 13.88万 - 项目类别:
Susceptibility and Resilience to Adverse Childhood Experiences: A Role for Perineuronal Nets
对童年不良经历的敏感性和恢复力:神经周围网络的作用
- 批准号:
10221013 - 财政年份:2020
- 资助金额:
$ 13.88万 - 项目类别:
Susceptibility and Resilience to Adverse Childhood Experiences: A Role for Perineuronal Nets
对童年不良经历的敏感性和恢复力:神经周围网络的作用
- 批准号:
10458512 - 财政年份:2020
- 资助金额:
$ 13.88万 - 项目类别:
Susceptibility and Resilience to Adverse Childhood Experiences: A Role for Perineuronal Nets
对童年不良经历的敏感性和恢复力:神经周围网络的作用
- 批准号:
10667529 - 财政年份:2020
- 资助金额:
$ 13.88万 - 项目类别:
An animal model for developing treatments of PTSD core features
用于开发 PTSD 核心特征治疗方法的动物模型
- 批准号:
7770864 - 财政年份:2009
- 资助金额:
$ 13.88万 - 项目类别:
An animal model for developing treatments of PTSD core features
用于开发 PTSD 核心特征治疗方法的动物模型
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8034707 - 财政年份:2009
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$ 13.88万 - 项目类别:
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在模型系统中开发过度觉醒的治疗方法
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9223738 - 财政年份:2009
- 资助金额:
$ 13.88万 - 项目类别:
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用于开发 PTSD 核心特征治疗方法的动物模型
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7573209 - 财政年份:2009
- 资助金额:
$ 13.88万 - 项目类别:
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