Metals and Developmental Origins of Late Life Cognitive Function
金属与晚年认知功能的发育起源
基本信息
- 批准号:10027714
- 负责人:
- 金额:$ 54.54万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-08 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AblationAccountingAddressAdultAgeAlzheimer&aposs DiseaseAmericanAnimal ExperimentationAnimalsBiological MarkersBloodBlood specimenCellsChildCognitiveCognitive agingCohort StudiesDataDementiaDental EnamelDepositionDevelopmentDiseaseEconomic BurdenElderlyEncapsulatedEnrollmentEnvironmental ExposureEpigenetic ProcessExposure toFluorescenceGene ExpressionGenetic TranscriptionHealthHumanImpaired cognitionIndividualInductively Coupled Plasma Mass SpectrometryInterventionLasersLifeLinkLipid BilayersMeasuresMetal exposureMetalsMicroRNAsModificationNeuronsOutcomeParticipantPathologyPatientsPerformancePopulationPreventionProcessPublic HealthQuestionnairesRiskRisk FactorsRoentgen RaysRoleSamplingSerumSignal TransductionStructure of nail of toeTestingTimeTooth structureUnited StatesVulnerable PopulationsWomanWorkage relatedaging brainaging populationbasecognitive developmentcognitive functioncognitive testingcost estimateearly childhoodearly detection biomarkersearly life exposureeconomic costextracellular vesicleshuman studyin uterolead exposuremenmiRNA expression profilingnanoscalenovel markerparticlepostnatalprenatalrecruit
项目摘要
We propose to study the relation between prenatal, early postnatal, and adult exposure to metals and
cognitive function in older age, and whether early life exposures modify effects of adult exposures. We will also
explore whether those exposures and cognitive outcomes are associated with changes in blood-derived
extracellular vesicle (EV) micro RNA expression (miRNA), which could represent epigenetic mechanisms
underlying associations. We will conduct a cohort study among a subset of participants in the original St. Louis
Baby Tooth (SLBT) study who donated their baby teeth in the 1950s and 1960s. Based on our pilot work, we
anticipate easily being able to enroll 1,000 former SLBT participants (500 men and 500 women) who will have
completed questionnaires and cognitive function testing, and from whom we will collect blood for miRNA
analyses and repeated toenail samples for adult metal analyses. Prenatal and early postnatal exposure to
several metals will be assessed by measuring metals in baby tooth enamel (using laser-ablation inductively
coupled plasma mass spectrometry). Adult metal exposures will be assessed using X-Ray Fluorescence to
measure metals in the toenail samples. EVs will be isolated from the blood samples and analyzed for EV
miRNA expression levels. The SLBT provides a unique setting that will allow us to have individual-level
biomarkers of early life and adult metal exposures in older adults on whom we can conduct cognitive function
testing. This study setting allows us to have an unprecedented ability to examine whether early life exposures
are related to late life cognitive health—a hypothesis suggested for metals exposure from animal research, but
extremely hard to test in humans without the biomarker of such early exposure that the already collected baby
teeth in the SLBT can provide.
我们建议研究产前、产后早期和成人暴露于金属之间的关系,
老年人的认知功能,以及早年接触是否会改变成年人接触的影响。我们还将
探索这些暴露和认知结果是否与血液来源的变化有关,
细胞外囊泡(EV)微RNA表达(miRNA),这可能代表表观遗传机制
潜在的关联我们将在最初圣路易斯的一部分参与者中进行队列研究。
婴儿牙齿(SLBT)研究谁捐赠了他们的婴儿牙齿在20世纪50年代和60年代。根据我们的试点工作,我们
预计可以轻松招募1,000名前SLBT参与者(500名男性和500名女性),他们将
完成问卷调查和认知功能测试,我们将从他们那里收集血液进行miRNA检测,
分析和重复的趾甲样本进行成人金属分析。产前和产后早期接触
通过测量婴儿牙釉质中的金属(使用激光消融感应
偶联等离子体质谱法)。成人金属暴露将使用X射线荧光进行评估,
测量脚趾甲样本中的金属含量将从血液样本中分离EV并分析EV
miRNA表达水平。SLBT提供了一个独特的设置,使我们能够拥有个人级别的
我们可以对老年人的早期生命和成年金属暴露进行认知功能的生物标志物
试验.这项研究使我们有了前所未有的能力来检查生命早期的暴露是否
与晚年的认知健康有关--这是动物研究中提出的金属暴露假设,
如果没有这种早期暴露的生物标志物,
牙齿在SLBT可以提供。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Marc G Weisskopf其他文献
The opioid peptide dynorphin mediates heterosynaptic depression of hippocampal mossy fibre synapses and modulates long-term potentiation
阿片样肽强啡肽介导海马苔藓纤维突触的异突触抑制并调节长时程增强
- DOI:
10.1038/362423a0 - 发表时间:
1993-04-01 - 期刊:
- 影响因子:48.500
- 作者:
Marc G Weisskopf;Robert A Zalutsky;Roger A Nicoll - 通讯作者:
Roger A Nicoll
Marc G Weisskopf的其他文献
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{{ truncateString('Marc G Weisskopf', 18)}}的其他基金
Child and adult Metal exposures, gene expression and neuropathologically confirmed Alzheimer's Disease
儿童和成人金属暴露、基因表达和神经病理学证实的阿尔茨海默病
- 批准号:
10901032 - 财政年份:2023
- 资助金额:
$ 54.54万 - 项目类别:
Military exposures and ALS in a large veteran population
大量退伍军人中的军事暴露和 ALS
- 批准号:
10701049 - 财政年份:2022
- 资助金额:
$ 54.54万 - 项目类别:
Military exposures and ALS in a large veteran population
大量退伍军人中的军事暴露和 ALS
- 批准号:
10609998 - 财政年份:2022
- 资助金额:
$ 54.54万 - 项目类别:
International Society for Environmental Epidemiology (ISEE) Annual Conference
国际环境流行病学学会(ISEE)年会
- 批准号:
10432038 - 财政年份:2020
- 资助金额:
$ 54.54万 - 项目类别:
Pre-disease biomarkers of persistent organic pollutants, immune system, and amyotrophic lateral sclerosis
持久性有机污染物、免疫系统和肌萎缩侧索硬化症的病前生物标志物
- 批准号:
10438145 - 财政年份:2020
- 资助金额:
$ 54.54万 - 项目类别:
Metals and Developmental Origins of Late Life Cognitive Function
金属与晚年认知功能的发育起源
- 批准号:
10256790 - 财政年份:2020
- 资助金额:
$ 54.54万 - 项目类别:
Pre-disease biomarkers of persistent organic pollutants, immune system, and amyotrophic lateral sclerosis
持久性有机污染物、免疫系统和肌萎缩侧索硬化症的病前生物标志物
- 批准号:
10119592 - 财政年份:2020
- 资助金额:
$ 54.54万 - 项目类别:
Metals and Developmental Origins of Late Life Cognitive Function
金属与晚年认知功能的发育起源
- 批准号:
10653000 - 财政年份:2020
- 资助金额:
$ 54.54万 - 项目类别:
International Society for Environmental Epidemiology (ISEE) Annual Conference
国际环境流行病学学会(ISEE)年会
- 批准号:
10207644 - 财政年份:2020
- 资助金额:
$ 54.54万 - 项目类别:
Pre-disease biomarkers of persistent organic pollutants, immune system, and amyotrophic lateral sclerosis
持久性有机污染物、免疫系统和肌萎缩侧索硬化症的病前生物标志物
- 批准号:
10252748 - 财政年份:2020
- 资助金额:
$ 54.54万 - 项目类别:
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