Prenatal Alcohol and Neuroimmunity
产前酒精与神经免疫
基本信息
- 批准号:9093666
- 负责人:
- 金额:$ 21.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-07-01 至 2018-06-30
- 项目状态:已结题
- 来源:
- 关键词:AdolescenceAdolescentAdultAdverse effectsAlcohol consumptionAlcoholsAnimal ModelBirthChildClinical ResearchCommunicationCompetenceControl AnimalDataDepressed moodDevelopmentElderlyFetal Alcohol Spectrum DisorderFetusHealthImmuneImmune responseImmune systemImmunityImpairmentInfectionInflammationInflammatoryInflammatory ResponseLifeLife ExperienceLinkMalignant NeoplasmsMediatingMental DepressionMental HealthMicrogliaModelingMothersNatureNeuronal PlasticityNeurosecretory SystemsOrganismOutcomePersonal SatisfactionPhysiologicalPlayPrincipal InvestigatorRegulationReportingResearchRestRiskRoleStagingStressStudy modelsSystemWorkaddictionalcohol exposureclinical carecognitive functioncytokinefetalfetal programmingimmune functionimprovedinsightneurodevelopmentoffspringpregnantprenatalprogramsrelating to nervous system
项目摘要
DESCRIPTION (provided by applicant): Among the physiological abnormalities reported in fetal alcohol spectrum disorder (FASD), both clinical studies and studies using animal models and have demonstrated marked impairments in immune competence, including delayed and deficient development of the immune system, depressed or overactive immune responses to challenge, and increased risk for infection and various forms of cancer, with many changes persisting into adolescence and adulthood. Impaired immune function in the alcohol-consuming mother, altered immunity at the fetal-placental interface, and disruption of the finely-tuned bidirectional communication between the neuroendocrine and neuroimmune systems appear to play a role in the deficits observed in prenatal alcohol-exposed (PAE) offspring. The present proposal investigates when and how PAE can impact immune function, and will elucidate possible mechanisms underlying PAE's adverse effects on the mother, the fetus, and the interaction between maternal and fetal systems. The role of early life experience in programming the set-point or tone for stress and immune responsiveness to later life challenge will also be investigated. Our Specific Aims are: 1) To investigate the effects of alcohol consumption on neuroimmune function of the pregnant dam and fetus, and their possible link, in mediating alcohol-induced immune impairments in dams and PAE offspring via cytokine analysis (Expt 1A) and fetal microglia responsivity (Expt 1B). 2) To elucidate a developmental neuroimmune profile of PAE compared to control offspring from birth to adulthood to gain insight into how PAE, in the presence or absence of stress during the adolescent period, may differentially alter resting neuroimmune function and set the stage for vulnerability to stress or immune challenge in later life; 3) To investigate the role of early life immune challenge, imposed on an already sensitized organism (PAE), in modulating differential immune and neural outcomes of PAE and control animals following immune challenge in adulthood; 4) To elucidate mechanisms underlying the differential course of inflammation in PAE and control offspring observed previously, and to investigate possible differential effects of stress during adolescence, a sensitive developmental period, in modulating the course of inflammation in adulthood. Our working hypothesis is that fetal programming of stress and immune systems by PAE results in a primed, vulnerable pro-inflammatory-biased organism that is predisposed to increased responsiveness to immune challenge in adulthood. Elucidation of mechanisms underlying neuroimmune deficits in PAE offspring is critical for understanding the nature of the immune abnormalities seen in children with FASD, which will improve clinical care of these children, and ultimately improve their long-term health and well-being.
描述(申请人提供):在胎儿酒精谱系障碍(FASD)中报告的生理异常中,临床研究和使用动物模型的研究都证明了免疫能力的明显损害,包括免疫系统发育延迟和缺陷,对挑战的免疫应答抑制或过度活跃,以及感染和各种形式癌症的风险增加,许多变化持续到青春期和成年期。饮酒母亲的免疫功能受损,胎儿-胎盘界面的免疫功能改变,以及神经内分泌和神经免疫系统之间微调的双向通信中断,似乎在产前酒精暴露(PAE)后代中观察到的缺陷中发挥作用。 本提案调查PAE何时以及如何影响免疫功能,并将阐明PAE对母亲,胎儿以及母体和胎儿系统之间相互作用的不利影响的可能机制。早期生活经验在编程的设定点或音的压力和免疫反应,以后的生活挑战的作用也将被调查。我们的具体目标是:1)通过细胞因子分析(实验1A)和胎儿小胶质细胞反应性(实验1B)研究酒精摄入对妊娠母鼠和胎儿神经免疫功能的影响,以及它们在介导酒精诱导的母鼠和PAE后代免疫损伤中的可能联系。2)阐明PAE与对照后代从出生到成年的发育神经免疫特征,以深入了解PAE在青少年时期存在或不存在压力的情况下如何差异性地改变静息神经免疫功能,并为以后生活中对压力或免疫挑战的脆弱性奠定基础; 3)研究早期生命免疫攻击对已经致敏的生物体(PAE)的作用,在成年免疫攻击后调节PAE和对照动物的不同免疫和神经结果; 4)阐明先前观察到的PAE和对照后代中炎症过程差异的潜在机制,并研究青春期(敏感发育期)期间应激在调节成年期炎症过程中的可能差异效应。我们的工作假设是,胎儿编程的压力和免疫系统的PAE结果在一个启动,脆弱的促炎偏见的有机体,是倾向于增加响应性免疫挑战在成年期。阐明PAE后代神经免疫缺陷的潜在机制对于了解FASD儿童免疫异常的性质至关重要,这将改善这些儿童的临床护理,并最终改善他们的长期健康和福祉。
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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JOANNE WEINBERG其他文献
JOANNE WEINBERG的其他文献
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{{ truncateString('JOANNE WEINBERG', 18)}}的其他基金
Immune Dysregulation in FASD: Programming of health and neurobehavioral outcomes
FASD 中的免疫失调:健康和神经行为结果的规划
- 批准号:
10165416 - 财政年份:2017
- 资助金额:
$ 21.88万 - 项目类别:
Immune Dysregulation in FASD: Programming of health and neurobehavioral outcomes
FASD 中的免疫失调:健康和神经行为结果的规划
- 批准号:
9390574 - 财政年份:2017
- 资助金额:
$ 21.88万 - 项目类别:
PRENATAL ETHANOL EXPOSURE: PROGRAMMING, DNA METHYLATION AND THE HPS AXIS
产前乙醇暴露:编程、DNA 甲基化和 HPS 轴
- 批准号:
7295785 - 财政年份:2006
- 资助金额:
$ 21.88万 - 项目类别:
PRENATAL ETHANOL EXPOSURE: PROGRAMMING, DNA METHYLATION AND THE HPS AXIS
产前乙醇暴露:编程、DNA 甲基化和 HPS 轴
- 批准号:
7216586 - 财政年份:2006
- 资助金额:
$ 21.88万 - 项目类别:
IMMUNOREACTIVE EFFECTS OF FETAL ETHANOL EXPOSURE
胎儿乙醇暴露的免疫反应影响
- 批准号:
2045973 - 财政年份:1994
- 资助金额:
$ 21.88万 - 项目类别:
IMMUNOREACTIVE EFFECTS OF FETAL ETHANOL EXPOSURE
胎儿乙醇暴露的免疫反应影响
- 批准号:
2045972 - 财政年份:1994
- 资助金额:
$ 21.88万 - 项目类别:
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