Effect of Methamphetamine and/or HIV on Human iPSCs-derived microglia and Neuron

甲基苯丙胺和/或 HIV 对人 iPSC 衍生的小胶质细胞和神经元的影响

基本信息

  • 批准号:
    10031319
  • 负责人:
  • 金额:
    $ 23.78万
  • 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:
    2020-07-15 至 2022-06-30
  • 项目状态:
    已结题

项目摘要

Abstract METH, a potent addictive psychostimulant, is one of the most commonly abused drugs in the United States. METH abuse is highly prevalent in HIV-infected individuals, which presents unique challenges for HIV prevention and treatment. Given the overlap impact of METH use and HIV on neuronal damage in the CNS, it becomes urgent to understand the role of interplays between METH and HIV in the pathogenesis of HIV- associated neurocognitive disorders (HAND). However, studies of HAND have been hampered by difficulties in collecting primary microglial and neuronal cells from autopsy or biopsy of HIV patients. Recent success in generating microglia and neurons from human induced pluripotent stem cell lines (iPSCs) now offers a great opportunity to study the direct interactions between HIV-infected microglia and neurons. The proposed studies will use iPSC-derived microglia (iPSC-MG) and neuron (iPSC-N) to examine our overall hypothesis that METH and/or HIV inhibit the intracellular HIV restriction factors and induce the inflammasomes and neurotoxic miRNAs in iPSC-MG, which facilitate HIV infection/replication in iPSC-MG and promote the death of iPSC-N. We propose two specific aims to address this hypothesis: Aim 1 To determine whether METH enhances HIV infection/replication in iPSC-MG. Mechanistically, we will examine whether METH and/or HIV inhibit the intracellular HIV restriction factors in iPSC-MG; Aim 2 To determine whether METH and/or HIV infection induce expression of the inflammasomes and neurotoxic miRNAs in iPSC-MG and promote the death of IPSC-N. This project fits well to the NIDA’s recent interests in studying the impact of drug abuse and/or HIV on human iPSC-derived CNS cells. The information resulting from the proposed studies using the iPSC-MG and iPSC-N will provide important insights on how the interplays of two major pathologic factors (HIV and METH) in the CNS compromise the intracellular anti-HIV immunity of microglia and induce neuronal death, which are the key mechanisms for HIV infection/persistence in the brain and development of HAND.
摘要

项目成果

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WENZHE HO其他文献

WENZHE HO的其他文献

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{{ truncateString('WENZHE HO', 18)}}的其他基金

Target Host Epigenetic Regulation of HIV Proviruses to Reinforce Viral Deep Latency in Microglia
HIV原病毒的靶宿主表观遗传调控可增强小胶质细胞中病毒的深潜伏期
  • 批准号:
    10748760
  • 财政年份:
    2023
  • 资助金额:
    $ 23.78万
  • 项目类别:
Effect of Methamphetamine and/or HIV on Human iPSCs-derived microglia and Neuron
甲基苯丙胺和/或 HIV 对人 iPSC 衍生的小胶质细胞和神经元的影响
  • 批准号:
    10210377
  • 财政年份:
    2020
  • 资助金额:
    $ 23.78万
  • 项目类别:
HIV, Methamphetamine and Human iPSC-derived Microglia-containing Cerebral Organoids
HIV、甲基苯丙胺和人类 iPSC 衍生的含有小胶质细胞的大脑类器官
  • 批准号:
    10611364
  • 财政年份:
    2020
  • 资助金额:
    $ 23.78万
  • 项目类别:
HIV, Methamphetamine and Human iPSC-derived Microglia-containing Cerebral Organoids
HIV、甲基苯丙胺和人 iPSC 衍生的含有小胶质细胞的大脑类器官
  • 批准号:
    10205018
  • 财政年份:
    2020
  • 资助金额:
    $ 23.78万
  • 项目类别:
HIV, Methamphetamine and Human iPSC-derived Microglia-containing Cerebral Organoids
HIV、甲基苯丙胺和人 iPSC 衍生的含有小胶质细胞的大脑类器官
  • 批准号:
    10398189
  • 财政年份:
    2020
  • 资助金额:
    $ 23.78万
  • 项目类别:
HIV, Methamphetamine and Human iPSC-derived Microglia-containing Cerebral Organoids
HIV、甲基苯丙胺和人类 iPSC 衍生的含有小胶质细胞的大脑类器官
  • 批准号:
    10055449
  • 财政年份:
    2020
  • 资助金额:
    $ 23.78万
  • 项目类别:
Role of miRNAs in Methamphetamine/HIV-mediated Immune Activation
miRNA 在甲基苯丙胺/HIV 介导的免疫激活中的作用
  • 批准号:
    10357940
  • 财政年份:
    2018
  • 资助金额:
    $ 23.78万
  • 项目类别:
Opioids, Extracellular Vesicles and BBB Innate Immunity
阿片类药物、细胞外囊泡和 BBB 先天免疫
  • 批准号:
    9381158
  • 财政年份:
    2017
  • 资助金额:
    $ 23.78万
  • 项目类别:
Opioids, Extracellular Vesicles and BBB Innate Immunity
阿片类药物、细胞外囊泡和 BBB 先天免疫
  • 批准号:
    9485926
  • 财政年份:
    2017
  • 资助金额:
    $ 23.78万
  • 项目类别:
Methamphetamine, Innate Immunity and HIV
甲基苯丙胺、先天免疫和艾滋病毒
  • 批准号:
    9308910
  • 财政年份:
    2016
  • 资助金额:
    $ 23.78万
  • 项目类别:

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