Neuroimmune Cell Networks in Opioid Dependence and Withdrawal

阿片类药物依赖和戒断中的神经免疫细胞网络

基本信息

  • 批准号:
    8600490
  • 负责人:
  • 金额:
    $ 19.38万
  • 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 2015-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Chronic opioid use changes the brain's state, including neuroimmune activity, impacting brain function and behavior and contributing to continued drug dependence and pathology. However, there is little work examining the progression of the cytokine response during opioid dependence and withdrawal, a period of profound autonomic and emotional upset. Our recent published and preliminary data demonstrate a significant neuroimmune response during withdrawal. These findings suggest that an abrupt cessation of opioid intake leads to an acute central nervous system (CNS) inflammatory response in the central nucleus of the amygdala (CeA), a brain region neuroanatomically associated with affective and cardiorespiratory regulation. It is now reasonable to postulate a chain of proinflammatory responses in a network involving vascular, glial and neuronal cells that comprise this tissue. We propose to now extend the approach developed for this prior work to the specific question of whether similar multi-cell type tissue inflammatory processes underlie opiate withdrawal. We propose a high-dimensional systematic investigation of the CeA inflammatory response in an in vivo rat model of withdrawal aiming to understanding the cell-type specific and molecular framework for neuroinflammatory responses. This will provide potential for improved treatment of opiate withdrawal and its associated pathology. The investigators comprise a collaborative team with the expertise required for this experimental design and analysis, including experts in the molecular effects of opiate exposure and withdrawal in the brain and computational biology and genomics expertise for collection of high dimensional datasets and their analysis and interpretation. We will collect transcriptional and protein data on the molecular and cellular network response in the CeA in order to characterize the cell-type specific contributions of vascular endothelial cells, glia, monocyte lineage cells and neurons to the tissue response. These data will reveal the molecular networks altered within the cell types, their impact on the tissue as a whole, and the resultant neuroinflammatory pathology and neuronal effects that contribute to acute opioid withdrawal's symptomatology.
描述(由申请人提供):长期使用阿片类药物会改变大脑的状态,包括神经免疫活动,影响大脑功能和行为,并导致持续的药物依赖和病理。然而,很少有人研究阿片类药物依赖和戒断期间细胞因子反应的进展,这是一个严重的自主神经和情绪不安的时期。我们最近发表的初步数据表明,戒断期间存在显着的神经免疫反应。这些发现表明,突然停止阿片类药物摄入会导致杏仁核(CeA)中央核发生急性中枢神经系统(CNS)炎症反应,杏仁核是一个在神经解剖学上与情感和心肺调节相关的大脑区域。现在可以合理地假设,在涉及构成该组织的血管、神经胶质细胞和神经元细胞的网络中存在一系列促炎反应。我们现在建议将先前工作开发的方法扩展到以下具体问题:类似的多细胞类型组织炎症过程是否是阿片戒断的基础。我们提出对体内戒断大鼠模型中的 CeA 炎症反应进行高维系统研究,旨在了解神经炎症反应的细胞类型特异性和分子框架。这将为改善阿片戒断及其相关病理的治疗提供潜力。研究人员组成了一个协作团队,拥有实验设计和分析所需的专业知识,其中包括阿片类药物暴露和戒断对大脑的分子影响方面的专家,以及用于收集高维数据集及其分析和解释的计算生物学和基因组学专业知识。我们将收集有关 CeA 中分子和细胞网络反应的转录和蛋白质数据,以便表征血管内皮细胞、神经胶质细胞、单核细胞谱系细胞和神经元对组织反应的细胞类型特异性贡献。这些数据将揭示细胞类型内改变的分子网络、它们对整个组织的影响,以及由此产生的导致急性阿片类药物戒断症状的神经炎症病理学和神经元效应。

项目成果

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JAMES SCHWABER其他文献

JAMES SCHWABER的其他文献

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{{ truncateString('JAMES SCHWABER', 18)}}的其他基金

Molecular Neurogenetics of the Brainstem Neuronal Source of Cardioprotective Vagal Outflow
心脏保护性迷走神经流出脑干神经源的分子神经遗传学
  • 批准号:
    10522387
  • 财政年份:
    2022
  • 资助金额:
    $ 19.38万
  • 项目类别:
Molecular Neurogenetics of the Brainstem Neuronal Source of Cardioprotective Vagal Outflow
心脏保护性迷走神经流出脑干神经源的分子神经遗传学
  • 批准号:
    10641909
  • 财政年份:
    2022
  • 资助金额:
    $ 19.38万
  • 项目类别:
Multiscale Model of the Vagal Outflow to the Heart
迷走神经流出心脏的多尺度模型
  • 批准号:
    9908155
  • 财政年份:
    2017
  • 资助金额:
    $ 19.38万
  • 项目类别:
Multiscale Model of the Vagal Outflow to the Heart
迷走神经流出心脏的多尺度模型
  • 批准号:
    9152617
  • 财政年份:
    2017
  • 资助金额:
    $ 19.38万
  • 项目类别:
Neuroimmune Cell Networks in Opioid Dependence and Withdrawal
阿片类药物依赖和戒断中的神经免疫细胞网络
  • 批准号:
    8676771
  • 财政年份:
    2013
  • 资助金额:
    $ 19.38万
  • 项目类别:
Modeling Central Autonomic Regulatory Network Adaptation to Hypertension
中央自主调节网络对高血压的适应建模
  • 批准号:
    8502346
  • 财政年份:
    2012
  • 资助金额:
    $ 19.38万
  • 项目类别:
Modeling Central Autonomic Regulatory Network Adaptation to Hypertension
中央自主调节网络对高血压的适应建模
  • 批准号:
    8372524
  • 财政年份:
    2012
  • 资助金额:
    $ 19.38万
  • 项目类别:
Modeling Central Autonomic Regulatory Network Adaptation to Hypertension
中央自主调节网络对高血压的适应建模
  • 批准号:
    8843930
  • 财政年份:
    2012
  • 资助金额:
    $ 19.38万
  • 项目类别:
Modeling Central Autonomic Regulatory Network Adaptation to Hypertension
中央自主调节网络对高血压的适应建模
  • 批准号:
    8657102
  • 财政年份:
    2012
  • 资助金额:
    $ 19.38万
  • 项目类别:
Novel Low Cost, High Throughput DNA Sequencing Platform
新型低成本、高通量 DNA 测序平台
  • 批准号:
    7989338
  • 财政年份:
    2009
  • 资助金额:
    $ 19.38万
  • 项目类别:

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