Neonatal Opioid Exposure and Withdrawal: Molecular and Behavioral Consequences
新生儿阿片类药物暴露和戒断:分子和行为后果
基本信息
- 批准号:9911467
- 负责人:
- 金额:$ 71.08万
- 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:2020-04-01 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdenineAdultAffectAffinity ChromatographyAllelesAnimal ModelAnti-Inflammatory AgentsAreaBehaviorBehavioralBiological AssayBiological Response ModifiersBrain regionCanis familiarisCellsClinicalComplexCryingDataDevelopmentDiarrheaDistressEarly DiagnosisEarly treatmentEnterobacteria phage P1 Cre recombinaseEnvironmentExhibitsExposure toGenesGeneticGenetic Predisposition to DiseaseGenomicsGenotypeGuanineHeroinHospitalsHourHumanImmuneImmune responseImmunosuppressionInfantInnate Immune ResponseInnate Immune SystemLeadLength of StayLifeLinkLymphokinesMeasuresMediatingMessenger RNAMethadoneMicrogliaModelingMolecularMorphineMusNatural ImmunityNeonatalNeonatal Abstinence SyndromeNeuroimmune systemNewborn InfantNucleus AccumbensOpiate AddictionOpioidOpioid ReceptorPainPathway interactionsPerinatal ExposurePeripheralPharmaceutical PreparationsPharmacological TreatmentPhenotypePolypharmacyPregnant WomenPresynaptic TerminalsPublic HealthReceptor CellReceptor GeneRegulationRibosomesRiskRoleSeizuresSeveritiesSingle Nucleotide PolymorphismSleeplessnessSyndromeTestingTherapeuticTimeTooth structureTranslatingTremorUnited StatesWeight GainWild Type MouseWithdrawalWithdrawal Symptombasecomplement systemcytokineexperienceexperimental studygastrointestinalgene discoverygenetic risk factorgenomic variationhigh riskin uteroinsightinterestmidbrain central gray substancemolecular markermouse modelmu opioid receptorsneonateneuroinflammationneuronal cell bodynew technologynovelnovel therapeuticsopioid epidemicopioid exposureopioid useopioid withdrawalpupresponsetranscriptome
项目摘要
Project Summary
Opioid use among pregnant women is a growing public health concern in the United
States. Infants exposed to opioids in utero are at high risk of exhibiting Neonatal Opioid
Withdrawal Syndrome (NOWS), a combination of physical withdrawal symptoms including
high pitched crying, sleeplessness, irritability, gastrointestinal distress, and in the worst
cases, seizures. The complexity of this syndrome is amplified by a variety of clinical factors
such as duration of maternal opioid exposure, maternal polypharmacy, environment, and
genetics. The complexity of in utero opioid exposure and NOWS make it very difficult to
investigate underlying molecular mechanisms that could ultimately inform early diagnosis
and treatment. Therefore, we have developed a much needed mouse model of 3-
trimester opioid exposure and withdrawal. Based on preliminary evidence, we hypothesize
that microglia activation and immune mediators contribute to the severity of NOWS and
a common SNP in the -opioid receptor modulates these effects. Using morphine as a
prototypical opioid, we will exploit our model to test these hypotheses. First we will fully
characterize the role of the innate immune system in NOWS and determine if regulation
of neuroinflammation has therapeutic potential by pharmacological treatment with the anti-
inflammatory drug, ibudilast. Second, as recent clinical findings suggest that genomic
variation in the gene that encodes the -opioid receptor (Oprm1 A118G) may influence
NOWS severity, we will use our mouse line that contains the equivalent Oprm1 A118G
SNP to determine the impact of Oprm1 genetics on microglia activation and immune
mediators. Using our model of 3-trimester opioid exposure and withdrawal we will use
TRAP-Seq, a new technology for retrieving mRNAs within the ribosomal complex that are
actively being translated, in our case in cells expressing m-opioid receptors, to interrogate
the changing transcriptome following opioid exposure and withdrawal. This project is likely
to have a sustained and powerful impact on the field because we will address
mechanisms through which perinatal exposure to opiates results in NOWS, and how
genetics and immune response contribute.
项目总结
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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Julie A Blendy其他文献
Julie A Blendy的其他文献
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{{ truncateString('Julie A Blendy', 18)}}的其他基金
Low-input profiling of brain-region and cell-type specific epigenomic dynamics to understand gene-environment interactions in opioid addiction
对大脑区域和细胞类型特异性表观基因组动力学进行低输入分析,以了解阿片类药物成瘾中的基因与环境的相互作用
- 批准号:
10605801 - 财政年份:2023
- 资助金额:
$ 71.08万 - 项目类别:
Mapping opioid-dependence state transitions across structural, functional, and transcriptomic topologies
绘制结构、功能和转录组拓扑中阿片类药物依赖性状态转变的图谱
- 批准号:
10293782 - 财政年份:2021
- 资助金额:
$ 71.08万 - 项目类别:
Mapping opioid-dependence state transitions across structural, functional, and transcriptomic topologies
绘制结构、功能和转录组拓扑中阿片类药物依赖性状态转变的图谱
- 批准号:
10493185 - 财政年份:2021
- 资助金额:
$ 71.08万 - 项目类别:
Mapping opioid-dependence state transitions across structural, functional, and transcriptomic topologies
绘制结构、功能和转录组拓扑中阿片类药物依赖性状态转变的图谱
- 批准号:
10622531 - 财政年份:2021
- 资助金额:
$ 71.08万 - 项目类别:
Neonatal Opioid Exposure and Withdrawal: Molecular and Behavioral Consequences
新生儿阿片类药物暴露和戒断:分子和行为后果
- 批准号:
10347354 - 财政年份:2020
- 资助金额:
$ 71.08万 - 项目类别:
Neonatal Opioid Exposure and Withdrawal: Molecular and Behavioral Consequences
新生儿阿片类药物暴露和戒断:分子和行为后果
- 批准号:
10552037 - 财政年份:2020
- 资助金额:
$ 71.08万 - 项目类别:
AMP-activated protein kinase (AMPK) and nicotine dependence
AMP 激活蛋白激酶 (AMPK) 和尼古丁依赖性
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9441755 - 财政年份:2016
- 资助金额:
$ 71.08万 - 项目类别:
T32 Translational Addiction Research Fellowship Program
T32 转化成瘾研究奖学金计划
- 批准号:
10159223 - 财政年份:2010
- 资助金额:
$ 71.08万 - 项目类别:
T32 Translational Addiction Research Fellowship Program
T32 转化成瘾研究奖学金计划
- 批准号:
10628649 - 财政年份:2010
- 资助金额:
$ 71.08万 - 项目类别:
T32 Translational Addiction Research Fellowship Program
T32 转化成瘾研究奖学金计划
- 批准号:
10400087 - 财政年份:2010
- 资助金额:
$ 71.08万 - 项目类别:
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