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

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
  • 批准号:
    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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腺嘌呤核苷酸转位酶在慢性阻塞性肺病(COPD)线粒体功能相关衰老中的作用
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Pathways of Succinate Accumulation and Adenine Nucleotide Depletion in Cardiac Ischemia
心脏缺血中琥珀酸积累和腺嘌呤核苷酸消耗的途径
  • 批准号:
    10534031
  • 财政年份:
    2022
  • 资助金额:
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  • 项目类别:
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使用 FRET 开发 miRNA 和腺嘌呤甲基转移酶的诺贝尔检测方法
  • 批准号:
    21K05120
  • 财政年份:
    2021
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  • 批准号:
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    2021
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    $ 71.08万
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DNA Methylation at N6-Adenine in Placental Trophoblast Development
胎盘滋养层发育中 N6-腺嘌呤 DNA 甲基化
  • 批准号:
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DNA Methylation at N6-Adenine in Placental Trophoblast Development
胎盘滋养层发育中 N6-腺嘌呤 DNA 甲基化
  • 批准号:
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胎盘滋养层发育中 N6-腺嘌呤 DNA 甲基化
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    10226235
  • 财政年份:
    2020
  • 资助金额:
    $ 71.08万
  • 项目类别:
DNA Methylation at N6-Adenine in Placental Trophoblast Development
胎盘滋养层发育中 N6-腺嘌呤 DNA 甲基化
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    10396102
  • 财政年份:
    2020
  • 资助金额:
    $ 71.08万
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胎盘滋养层发育中 N6-腺嘌呤 DNA 甲基化
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