Role of exosomes in ethanol-induced neurotoxicity
外泌体在乙醇诱导的神经毒性中的作用
基本信息
- 批准号:10266778
- 负责人:
- 金额:$ 35.1万
- 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:2020-09-20 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AdultAdverse effectsAlcohol-Induced NeurotoxicityAlcoholsAnimal ModelAnimalsAnxietyApoptosisApoptoticAstrocytesBehaviorBehavioralBiogenesisBloodBody FluidsBrainCell DeathCell MaturationCell membraneCellsCerebrospinal FluidCessation of lifeChildChronicClinicalClinical ResearchClustered Regularly Interspaced Short Palindromic RepeatsCognitiveCommunicationComplementCorticosteroneCorticotropinDefectEmotional DisturbanceEndothelial CellsEnzyme-Linked Immunosorbent AssayEthanolFetal Alcohol ExposureFetal Alcohol Spectrum DisorderGenesGenomicsGrowthHomeostasisHormonalHumanHuman MilkHypothalamic structureImmuneIn SituIn VitroIndividualInfant formulaInflammatoryIntegral Membrane ProteinLaboratory RatLaboratory miceLeadLearning DisabilitiesLipid BilayersLipidsMeasurementMeasuresMembrane LipidsMental disordersMicroRNAsMicrogliaModelingMood DisordersNamesNeuraxisNeurobiologyNeurogliaNeurologicNeuronsNewborn InfantOligodendrogliaOligonucleotidesOxidative StressPOMC genePathway interactionsPatientsPeptidesPhysiologicalPlayPopulationPregnancyPrevalencePro-OpiomelanocortinProblem behaviorProductionPropertyProteinsProteomicsRNARattusRegulationReportingResearchReverse Transcriptase Polymerase Chain ReactionRoleSamplingSeriesSignal PathwaySignal TransductionStressStructureTechniquesTestingThird Pregnancy TrimesterTissuesTransplantationUnited StatesUrineVesicleWestern Blottingalcohol exposureanxiety-like behaviorbasebeta-Endorphinbiological adaptation to stresscell behaviorcell typechemokinecytokinedietary controlexosomeexperienceextracellular vesiclesfetalgenomic datahypothalamic-pituitary-adrenal axisimmune functionin vivoknock-downmicrovesiclesmonocytenerve stem cellneuron apoptosisneuron lossneurotoxicityneurotransmissionnovelnovel therapeutic interventionparticlepostnatalpostnatal periodpre-clinicalprenatalpreventresponsesocioeconomicsstemstem cell growththerapeutically effectiveuptake
项目摘要
Fetal alcohol spectrum disorders (FASD) include a range of maladies caused by chronic alcohol exposure
during pregnancy. It is documented that approximately 2% to 5% of children born in the United States have
FASD. Clinical studies have shown children and adults with FASD often show hyperresponsiveness to stress
and are vulnerable to psychiatric disorders, particularly mood disorders. The neurobiology of these emotional
disturbances are not well understood, but studies utilizing animal models of fetal alcohol exposure have shown
that prenatal or early-postnatal ethanol exposure in laboratory rats and mice disrupts the hypothalamic-
pituitary-adrenal axis function and its physiological response to stress and promotes anxiety-like behaviors.
Both prenatal ethanol exposure and postnatal ethanol exposure induce hypothalamic proopiomelanocortin
neuronal death and reduce levels of proopiomelanocortin and its peptide product β-endorphin, as well as the β-
endorphin peptide's inhibitory control of the hypothalamic-pituitary-adrenal axis function. Replenishment of β-
endorphin neurons via neuronal transplantation prevents stress and behavioral problems in fetal alcohol-
exposed
animals, indicating that β-endorphin deficiency is a significant contributor to the stress and behavioral
abnormalities in these animals. The mechanism by which β-endorphin neurons experience apoptosis following
fetal alcohol exposure is not well understood. There are several preclinical and clinical evidences that
suggest microglia, one of the immune cells in the central nervous system, play a major role in the regulation of
alcohol-induced neuronal damage. Recent studies show that inflammatory cytokines can be released in
association with small extracellular vesicles, called exosomes, from microglia. These exosomes are comprised
of a lipid bilayer, transmembrane proteins, and cytosolic components derived from their host cells. However,
the role of microglial exosomes in alcohol-induced neurotoxicity has not been well studied. In this proposal, we
propose to determine if microglia use exosomes to induce ethanol-induced β-endorphin neuronal death and
stress axis functions. We also propose to use proteomic and genomic measurements to identify if ethanol
treatment during the postnatal period increases levels of chemokines, complements, and microRNAs in
microglial exosomes. Additionally, we propose to identify the exosome biomolecules that have apoptotic effects
on β-endorphin neurons. Together these studies should establish how prenatal ethanol modifies contents of
proteins and genes within exosomes to induce β-endorphin neuronal apoptosis that may lead to stress axis
hyperresponsiveness and increased anxiety behavior. Additionally, the proposed studies may identify a novel
therapeutic approach to prevent some of the neurological problems that occur in FASD patients.
胎儿酒精谱系障碍(FASD)包括一系列由慢性酒精暴露引起的疾病
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)
专利数量(0)
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DIPAK KUMAR SARKAR其他文献
DIPAK KUMAR SARKAR的其他文献
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{{ truncateString('DIPAK KUMAR SARKAR', 18)}}的其他基金
Role of exosomes in ethanol-induced neurotoxicity
外泌体在乙醇诱导的神经毒性中的作用
- 批准号:
10095400 - 财政年份:2020
- 资助金额:
$ 35.1万 - 项目类别:
Role of exosomes in ethanol-induced neurotoxicity
外泌体在乙醇诱导的神经毒性中的作用
- 批准号:
10473743 - 财政年份:2020
- 资助金额:
$ 35.1万 - 项目类别:
Role of SRY in transgenerational transmission of alcohol epigenetic marks on proopiomelanocortin gene
SRY在阿黑皮素原基因酒精表观遗传标记跨代传递中的作用
- 批准号:
10190731 - 财政年份:2017
- 资助金额:
$ 35.1万 - 项目类别:
Targeting the Opioidergic and Adrenergic Systems to Control Breast Cancers
针对阿片能和肾上腺素能系统来控制乳腺癌
- 批准号:
10153710 - 财政年份:2017
- 资助金额:
$ 35.1万 - 项目类别:
Role of SRY in transgenerational transmission of alcohol epigenetic marks on proopiomelanocortin gene
SRY在阿黑皮素原基因酒精表观遗传标记跨代传递中的作用
- 批准号:
9382377 - 财政年份:2017
- 资助金额:
$ 35.1万 - 项目类别:
Fetal alcohol, estrogen-regulated genes and prostate cancer
胎儿酒精、雌激素调节基因和前列腺癌
- 批准号:
8974973 - 财政年份:2015
- 资助金额:
$ 35.1万 - 项目类别:
Fetal alcohol, estrogen-regulated genes and prostate cancer
胎儿酒精、雌激素调节基因和前列腺癌
- 批准号:
9107765 - 财政年份:2015
- 资助金额:
$ 35.1万 - 项目类别:
Biology of the NK cell cytolytic activity rhythm
NK 细胞溶细胞活性节律的生物学
- 批准号:
7523544 - 财政年份:2009
- 资助金额:
$ 35.1万 - 项目类别:
Fetal Alcohol Effects on Circadian clocks and POMC
胎儿酒精对生物钟和 POMC 的影响
- 批准号:
7856010 - 财政年份:2009
- 资助金额:
$ 35.1万 - 项目类别:
Biology of the NK cell cytolytic activity rhythm
NK 细胞溶细胞活性节律的生物学
- 批准号:
7895704 - 财政年份:2009
- 资助金额:
$ 35.1万 - 项目类别:
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