Neuroimaging Adaptive Microglia Processes During Extended Alcohol Drinking
长期饮酒期间的神经影像适应性小胶质细胞过程
基本信息
- 批准号:10511295
- 负责人:
- 金额:$ 12.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-13 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAlcohol consumptionAlcoholsAnimalsAttenuatedBindingBrainBrain imagingCellsChronicComplexConflict (Psychology)DataDevelopmentDoseFutureGoalsHumanImageImaging DeviceImmuneImmune responseImmune signalingImmune systemIn VitroLeadLinkMacrophage Colony-Stimulating FactorMacrophage Colony-Stimulating Factor ReceptorMeasuresMediatingMicrogliaNeuroimmunePersonsPhasePopulationPositron-Emission TomographyPrimatesProcessPropertyProteinsRodentSelf AdministrationSignaling ProteinSpecificityStimulusTestingTimeTranslatingalcohol exposurealcohol responsealcohol sensitivityalcohol use disorderalcohol use initiationbasedrinkingdrinking behaviorexperiencehigh riskimaging propertiesin vivoin vivo evaluationneuroimagingnonhuman primatenovelpre-clinicalpredicting responseprocess repeatabilityradiotracerresponsetooltranslation to humans
项目摘要
PROJECT SUMMARY
Acute alcohol triggers an immune response in the brain. A hallmark of this response is the activation of the
brain's primary immune cells, microglia. Microglia readily adapt to repeated stimuli, which can enhance or
attenuate microglia responses over time. However, preclinical findings characterizing these effects are highly
mixed depending on species, dose, alcohol chronicity, and timing. It is important to characterize adaptive
microglia processes during repeated alcohol exposures because innate neuroimmune factors are linked with
escalating alcohol drinking. Yet, these mechanisms cannot be evaluated yet in primates due to limited
noninvasive tools that measure microglia responses to acute immune challenges. This 2-phase proposal will
first develop a novel positron emission tomography (PET) radiotracer specific for the colony stimulating factor 1
receptor (CSF1R) that will characterize microglia dynamics from repeated alcohol exposures. CSF1R is
advantageous over current PET targets because it is expressed exclusively on microglia. This CSF1R PET
radiotracer will be evaluated for suitable imaging properties and sensitivity to an acute alcohol challenge.
Confirmation of these properties will provide a key tool for the second phase. Phase 2 will use this imaging tool
to measure the acute immune response to alcohol in nonhuman primates at three time points: alcohol naïve, a
week after initial alcohol challenge, and after 4 months alcohol self-administration. The data collected will
characterize adaptive microglia processes occur during alcohol initiation and escalating drinking, and
determine the relationship of these process with drinking behaviors. The findings will advance the field by
providing a new imaging tool ripe for translation to human studies while testing important hypotheses regarding
dynamic microglia processes from alcohol exposure and their effects on drinking behaviors. The results will
have clear translational implications for future human studies evaluating adaptive microglia processes in
people with alcohol use disorder and populations with high risk for future alcohol use disorder.
项目摘要
急性酒精会引发大脑的免疫反应。这种反应的一个标志是激活了
大脑的主要免疫细胞小胶质细胞小胶质细胞容易适应重复的刺激,这可以增强或
随着时间的推移减弱小胶质细胞的反应。然而,表征这些效应的临床前研究结果是高度相关的。
根据物种、剂量、酒精慢性和时间混合。重要的是要描述适应性
小胶质细胞在反复酒精暴露过程中的作用,因为先天性神经免疫因素与
不断增加的酒精摄入量然而,这些机制还不能在灵长类动物中进行评估,由于有限的
非侵入性工具,测量小胶质细胞对急性免疫挑战的反应。这两个阶段的提案将
首先开发一种新的特异于殖民地刺激因子1的正电子发射断层扫描(PET)放射性示踪剂
受体(CSF1R),将表征小胶质细胞的动力学反复酒精暴露。CSF1R是
因为它仅在小胶质细胞上表达,所以它比当前的PET靶标更有利。CSF1R PET
将评价放射性示踪剂的适当成像特性和对急性酒精激发的敏感性。
这些特性的确认将为第二阶段提供一个关键工具。第二阶段将使用这种成像工具
在三个时间点测量非人灵长类动物对酒精的急性免疫反应:未接触酒精的,
在初始酒精挑战后一周,以及在4个月酒精自我给药后。收集的数据将
表征在酒精起始和逐步饮酒期间发生的适应性小胶质细胞过程,以及
确定这些过程与饮酒行为的关系。这些发现将推动该领域的发展,
提供了一个新的成像工具,成熟的翻译为人类研究,同时测试重要的假设,
酒精暴露的动态小胶质细胞过程及其对饮酒行为的影响。结果将
对未来评估适应性小胶质细胞过程的人类研究具有明确的翻译意义,
患有酒精使用障碍的人和未来酒精使用障碍的高风险人群。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Ansel Hillmer其他文献
Ansel Hillmer的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Ansel Hillmer', 18)}}的其他基金
Neuroimaging Cholinergic Mechanisms of Fear Extinction in PTSD
PTSD 恐惧消退的神经影像学胆碱能机制
- 批准号:
10734244 - 财政年份:2023
- 资助金额:
$ 12.41万 - 项目类别:
Neuroimaging Adaptive Microglia Processes During Extended Alcohol Drinking
长期饮酒期间的神经影像适应性小胶质细胞过程
- 批准号:
10704077 - 财政年份:2022
- 资助金额:
$ 12.41万 - 项目类别:
Multimodal Neuroimaging of Alcohol Withdrawal: The Role of Glutamate in Neural Reorganization
酒精戒断的多模式神经影像学:谷氨酸在神经重组中的作用
- 批准号:
10092045 - 财政年份:2017
- 资助金额:
$ 12.41万 - 项目类别:
相似海外基金
Molecular mechanisms of carcinogenesis and symptoms associated with alcohol consumption
致癌的分子机制和饮酒相关症状
- 批准号:
23K05734 - 财政年份:2023
- 资助金额:
$ 12.41万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The investigation of chronic alcohol consumption enhanced aging colon in elder mice and the mechanism of suppressed on aging colon tissues by sesame lignans continuous intake
长期饮酒促进老年小鼠结肠衰老的研究及持续摄入芝麻木脂素抑制结肠组织衰老的机制
- 批准号:
23K10904 - 财政年份:2023
- 资助金额:
$ 12.41万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Internal Sources of Minority Stress and Alcohol Consumption
少数群体压力和饮酒的内部根源
- 批准号:
10742318 - 财政年份:2023
- 资助金额:
$ 12.41万 - 项目类别:
Characterizing the Relationship Between Alcohol Consumption and Neuron-Derived Exosomal MicroRNA Cargo in an Adolescent-Young Adult Twin Cohort
青少年双胞胎队列中酒精消耗与神经元衍生的外泌体 MicroRNA 货物之间关系的表征
- 批准号:
10452928 - 财政年份:2022
- 资助金额:
$ 12.41万 - 项目类别:
Endocrine regulation of alcohol consumption and fear learning
饮酒和恐惧学习的内分泌调节
- 批准号:
10483780 - 财政年份:2022
- 资助金额:
$ 12.41万 - 项目类别:
The impact of friends sharing different modalities of alcohol-related social media content on alcohol consumption: A longitudinal examination of changes in content shared by social networks over time
朋友分享不同形式的酒精相关社交媒体内容对饮酒的影响:对社交网络分享内容随时间变化的纵向研究
- 批准号:
10534428 - 财政年份:2022
- 资助金额:
$ 12.41万 - 项目类别:
Cannabis' Impact on Alcohol Consumption: Integrating Laboratory and Ecological Momentary Assessment Methods
大麻对酒精消费的影响:整合实验室和生态瞬时评估方法
- 批准号:
10339931 - 财政年份:2022
- 资助金额:
$ 12.41万 - 项目类别:
Chronic alcohol consumption results in elevated Autotaxin levels that suppress anti-tumor immunity
长期饮酒会导致自分泌运动因子水平升高,从而抑制抗肿瘤免疫力
- 批准号:
10370159 - 财政年份:2022
- 资助金额:
$ 12.41万 - 项目类别:
Cannabis' Impact on Alcohol Consumption: Integrating Laboratory and Ecological Momentary Assessment Methods
大麻对酒精消费的影响:整合实验室和生态瞬时评估方法
- 批准号:
10595096 - 财政年份:2022
- 资助金额:
$ 12.41万 - 项目类别:
Technology-based assessments and intervention to reduce alcohol consumption and improve HIV viral suppression in the Florida Cohort
基于技术的评估和干预,以减少佛罗里达队列的饮酒量并改善艾滋病病毒抑制
- 批准号:
10707386 - 财政年份:2022
- 资助金额:
$ 12.41万 - 项目类别: