Influence of Dietary Botanical Supplements on Biological and Behavioral Resilience
膳食植物补充剂对生物和行为弹性的影响
基本信息
- 批准号:9916523
- 负责人:
- 金额:$ 120万
- 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:2020-07-01 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AcidsAddressAffectAnimal ModelAnti-Inflammatory AgentsAnxietyBehaviorBehavioralBioavailableBiologicalBiological AvailabilityBiological MarkersBiological ModelsBiometryBlood - brain barrier anatomyBotanical dietary supplementsBotanicalsBrainCellsChronic stressClinicalClinical PharmacologyClinical TrialsClinical Trials DesignClinical assessmentsCognitiveComplementDataDietDietary PolyphenolDissectionDrug KineticsEndothelial CellsEventFeasibility StudiesFunctional disorderFutureGrantHumanImaging TechniquesImmuneImmune responseImmunosuppressionImpairmentInflammatoryInfrastructureInterdisciplinary StudyInterleukin-6Interneuron functionInterneuronsInvestigationLeukocytesMaintenanceMental DepressionMental HealthMicrogliaModelingMusNeuronsNucleus AccumbensPathogenesisPathway interactionsPeripheralPhenotypePhysiologicalPlasmaPredispositionPreparationProductionPropertyProtocols documentationPsychological StressRegulationResearchResearch DesignResearch Project GrantsResourcesRiskRodentRoleStressStress TestsSupplementationSynapsesSynaptic plasticitySystemTestingTissue SampleTissuesTrier Social Stress TestTumor-infiltrating immune cellsUp-RegulationValidationbiological adaptation to stressblood-brain barrier permeabilizationclinical developmentclinical investigationcohesioncytokinedata managementdepression modeldepressive symptomsdesignhuman tissueimmune functionin vivoinsightneuropsychiatric disorderpolyphenolpre-clinicalpreclinical studypreventprogramspsychologicquality assuranceresilienceresponsestress related disorderstressortranscriptome sequencing
项目摘要
Summary Abstract
The studies proposed in this U19 application titled “The Influence of Dietary Botanical Supplements on
Biological and Behavioral Resilience” represent a cohesive program of integrated and interdisciplinary
research approaches that comprehensively address the objectives and purpose of RFA-OD-19-001. In
particular, the principal objective of this botanical dietary supplement research center (BDSRC) is to provide
valuable insight, through both pre-clinical and clinical lines of investigation that may inform a future clinical trial
designed to determine if dietary polyphenol supplements can provide resilience against stress-induced
psychological impairment. We have shown through rigorous feasibility studies utilizing stress-induced models
of depression that supplementation with BDPP promotes resilience to depression-like behaviors. We have
identified biomolecular systems associated with immune function and neuronal activity that specific
bioavailable metabolites of BDPP influence to promote resilience to stress. We note that bioavailable
metabolites suppressed production of peripheral leukocytes derived inflammatory cytokines, in particular IL-6,
which is important to consider given studies that find production of IL-6 is a critical response that confers
susceptibility to stress. Whether or not metabolites of BDPP suppress the downstream pathophysiological
effects of stress-induced IL-6 that directly affect neuron function and behavior has yet to be established.
Therefore, Project 1 of this BDSRC will characterize if our botanical supplement provides resilience against
physiological pathways elicited by stress that are associated with increased IL-6 activity and that confer
susceptibility to the onset of depressive-like behavior. Project 1 will also identify biological targets in microglia,
interneurons, and blood brain barrier cells influenced by BDPP metabolites by state-of-the-art cell-specific
RNA-sequencing and imaging techniques. Project 2 will directly synergize with Project 1 by first providing an
assessment of the clinical properties of BDPP, and whether they parallel those observed in rodents. We will
conduct a pharmacokinetic and steady-state profile to define bioavailable metabolites found in human plasma,
and to confirm the presence of metabolites that exert biological effects against IL-6 production. Project 2 will
also utilize a multivariate adaptive regression splines model to identify specific metabolites or combinations of
BDPP metabolites responsible for modulating IL-6 expression. In addition, Project 2 will validate plasma IL-6
as a marker of biological resilience in response to BDPP treatment by testing if BDPP promotes resilience
against upregulation of plasma IL-6 in response to the Trier Social Stress Test in humans. The proposed
Projects are designed and optimized to synergize with each other, and to integrate seamlessly with the two
Scientific Cores. Together, this proposal offers to provide critical information of the mechanism of action and the
clinical properties of BDPP and its metabolites that fill the most critical gaps in the existing body of data needed
to optimally design a future clinical trial to test resilient properties of BDPP in response to stress.
总结抽象
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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James Warren Murrough其他文献
James Warren Murrough的其他文献
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{{ truncateString('James Warren Murrough', 18)}}的其他基金
Phase 1 Translational Diabetes Research Using The DYRK1A inhibitor, Harmine
使用 DYRK1A 抑制剂 Harmine 进行的 1 期转化糖尿病研究
- 批准号:
10665783 - 财政年份:2022
- 资助金额:
$ 120万 - 项目类别:
Phase 1 Translational Diabetes Research Using The DYRK1A inhibitor, Harmine
使用 DYRK1A 抑制剂 Harmine 进行的 1 期转化糖尿病研究
- 批准号:
10522566 - 财政年份:2022
- 资助金额:
$ 120万 - 项目类别:
Influence of Dietary Botanical Supplements on Biological and Behavioral Resilience
膳食植物补充剂对生物和行为弹性的影响
- 批准号:
10447072 - 财政年份:2020
- 资助金额:
$ 120万 - 项目类别:
Clinical Pharmacology and Target Validation of BDPP for Stress-Related Disorders
BDPP 治疗应激相关疾病的临床药理学和靶点验证
- 批准号:
10447074 - 财政年份:2020
- 资助金额:
$ 120万 - 项目类别:
Clinical Pharmacology and Target Validation of BDPP for Stress-Related Disorders
BDPP 治疗应激相关疾病的临床药理学和靶点验证
- 批准号:
10671054 - 财政年份:2020
- 资助金额:
$ 120万 - 项目类别:
Influence of Dietary Botanical Supplements on Biological and Behavioral Resilience
膳食植物补充剂对生物和行为弹性的影响
- 批准号:
10200685 - 财政年份:2020
- 资助金额:
$ 120万 - 项目类别:
Clinical Pharmacology and Target Validation of BDPP for Stress-Related Disorders
BDPP 治疗应激相关疾病的临床药理学和靶点验证
- 批准号:
10200687 - 财政年份:2020
- 资助金额:
$ 120万 - 项目类别:
Influence of Dietary Botanical Supplements on Biological and Behavioral Resilience
膳食植物补充剂对生物和行为弹性的影响
- 批准号:
10287962 - 财政年份:2020
- 资助金额:
$ 120万 - 项目类别:
Influence of Dietary Botanical Supplements on Biological and Behavioral Resilience
膳食植物补充剂对生物和行为弹性的影响
- 批准号:
10671047 - 财政年份:2020
- 资助金额:
$ 120万 - 项目类别:
Influence of Dietary Botanical Supplements on Biological and Behavioral Resilience
膳食植物补充剂对生物和行为弹性的影响
- 批准号:
10619086 - 财政年份:2020
- 资助金额:
$ 120万 - 项目类别:
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