Dietary Modulation of Neuroinflammation in Age-Related Memory Disorders
饮食调节与年龄相关的记忆障碍中的神经炎症
基本信息
- 批准号:9975668
- 负责人:
- 金额:$ 76.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-01 至 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:Active Biological TransportAgeAge-Related Memory DisordersAge-associated memory impairmentAgingAlzheimer&aposs DiseaseAmyotrophic Lateral SclerosisAntioxidantsBindingBloodBlood - brain barrier anatomyBlood PlateletsBlood PressureBrainBrain regionCellsClinicalClinical ResearchClinical TrialsCocoa PowderCognitive agingConsumptionDataDementiaDevelopmentDietDietary InterventionDietary intakeDiffusionElderlyEndothelial CellsEndotheliumEndotoxemiaEpidemicEquipmentFamilyFlavanolFoodFunctional Magnetic Resonance ImagingFunctional disorderGoalsHMGB1 geneHealthHealthcare SystemsHippocampus (Brain)HumanImmuneImpaired cognitionImpairmentIndividualInflammationInflammation MediatorsInflammatoryInnate Immune SystemIntakeInterventionInvestigationLearningLinkMeasurableMeasuresMediatingMediationMediator of activation proteinMemoryMemory impairmentMethodologyMicrogliaModelingNerve DegenerationNeurodegenerative DisordersOperative Surgical ProceduresOralOxidative StressParkinson DiseaseParticipantPathologyPathway interactionsPatientsPeripheralPeripheral NervesPilot ProjectsPlacebosPlantsPlasmaPopulationProductionQuality of lifeRandomized Controlled TrialsRecording of previous eventsReportingResearchRodentRodent ModelRoleSentinelSerologicalSerumSignal PathwaySignal TransductionStructureSynaptic plasticityTLR4 geneTNF geneTestingTraumaValidationVariantVasomotorage groupage relatedbasebeanbrain cellbrain dysfunctioncerebral blood volumecognitive functioncytokinedentate gyrusdietary supplementsepicatechinfunctional statusglymphatic systemgroup interventionhuman old age (65+)imaging approachimprovedimproved functioninginflammatory markerinsulin sensitivitymacrophageneurogenesisneuroinflammationneuronal survivalneuropathologynonhuman primatenutritional supplementationpost interventionpreventprimary outcomeprogramsprospectiveseptic patientsstem cellstherapeutic targetvascular inflammation
项目摘要
Within 25 years, the US population aged 65 and over will double in size to 80 million bringing, with it an
epidemic of aging-related cognitive decline, from normal cognitive aging to neurodegenerative disorders
including Alzheimer’s Disease (AD). These conditions impair quality of life and functional status, impose an
enormous burden on individuals, their families, the healthcare system, and require elucidation of mechanisms
and development of new treatments to prevent or at least slow their progression.
The use of plant-based food and drink for health purposes has a long and well-documented history. Cocoa
beans contain the flavanol epicatechin, an anti-oxidant with beneficial effects on blood pressure, endothelium-
dependent vasomotor function, platelet reactivity, insulin sensitivity, vascular inflammation, and circulating
progenitor cells. Importantly, flavanols have neuroprotective effects, suppressing oxidative stress and
inflammation and promoting neurogenesis, neuronal survival and synaptic plasticity, all of which are relevant to
the pathophysiology of neurodegenerative disorders like AD, amyotrophic lateral sclerosis (ALS), and
Parkinson’s Disease (PD).
Evidence from humans, non-human primates, and rodents points to a role for the hippocampus and its
subregions in aging-related neurodegenerative disorders including AD. We recently reported that dietary
intake of cocoa flavanols increased hippocampal function, measured as fMRI cerebral blood volume (CBV) and
a pilot mediation analysis showed that cocoa flavanols led to a decrease in the sentinel pro-inflammatory
mediator HMGB1, an activator of the innate immune system. In turn, this decrease in HMGB1 was linked to
improved hippocampal function. Recent evidence implicates HMGB1 in cognitive decline and impairment.
HMGB1 binds to Toll-like receptor 4 (TLR4), triggering the production of pro-inflammatory cytokines including
TNFa via NFkB-dependent pathways. In rodent models of endotoxemia and surgical trauma, HMGB1
mediated hippocampal-dependent memory impairment similar to that seen in septic patients, an effect
eliminated by neutralizing HMGB1.
These data mechanistically link HMGB1 to neurodegenerative impairment, suggesting its potential as a
therapeutic target, consistent with evidence that amplified systemic inflammation is associated with a variety of
age-related pathologies including Alzheimer’s Disease. They strongly support our major hypothesis that cocoa
flavanols improve hippocampal function by their effects on neuroinflammation, specifically HMGB1, via a
TLR4-NFkB-TNFa signaling pathway. We propose to test this model in a randomized controlled trial of 146
participants, age 50-69, receiving high or low daily cocoa flavanol for 12 weeks. Such a trial has potential for
significant clinical impact.
在25年内,美国65岁及以上的人口将翻一番,达到8000万
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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Richard P SLOAN其他文献
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{{ truncateString('Richard P SLOAN', 18)}}的其他基金
Dietary Modulation of Neuroinflammation in Age-Related Memory Disorders
饮食调节与年龄相关的记忆障碍中的神经炎症
- 批准号:
10457914 - 财政年份:2018
- 资助金额:
$ 76.41万 - 项目类别:
Dietary Modulation of Neuroinflammation in Age-Related Memory Disorders
饮食调节与年龄相关的记忆障碍中的神经炎症
- 批准号:
9933182 - 财政年份:2018
- 资助金额:
$ 76.41万 - 项目类别:
Dietary Modulation of Neuroinflammation in Age-Related Memory Disorders
饮食调节与年龄相关的记忆障碍中的神经炎症
- 批准号:
9766169 - 财政年份:2018
- 资助金额:
$ 76.41万 - 项目类别:
Dietary Modulation of Neuroinflammation in Age-Related Memory Disorders
饮食调节与年龄相关的记忆障碍中的神经炎症
- 批准号:
10187474 - 财政年份:2018
- 资助金额:
$ 76.41万 - 项目类别:
Psychosocial Factors and Aging: Resting/Reflexive Cardiovascular Control
心理社会因素和衰老:静息/反射性心血管控制
- 批准号:
8532602 - 财政年份:2013
- 资助金额:
$ 76.41万 - 项目类别:
Exercise, aging, and cognition: Effect and mechanisms
运动、衰老和认知:效果和机制
- 批准号:
8526315 - 财政年份:2010
- 资助金额:
$ 76.41万 - 项目类别:
Exercise, Age-Related Memory Decline, and Hippocampal Function.
运动、与年龄相关的记忆衰退和海马功能。
- 批准号:
8325547 - 财政年份:2010
- 资助金额:
$ 76.41万 - 项目类别:
Exercise, aging, and cognition: Effect and mechanisms
运动、衰老和认知:效果和机制
- 批准号:
8723714 - 财政年份:2010
- 资助金额:
$ 76.41万 - 项目类别:
Exercise, aging, and cognition: Effect and mechanisms
运动、衰老和认知:效果和机制
- 批准号:
7986691 - 财政年份:2010
- 资助金额:
$ 76.41万 - 项目类别:
Exercise, Age-Related Memory Decline, and Hippocampal Function.
运动、与年龄相关的记忆衰退和海马功能。
- 批准号:
7986086 - 财政年份:2010
- 资助金额:
$ 76.41万 - 项目类别:
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