Neuron-Glia Mechanisms & Interactions Underlying Opioid Abuse-HIV-1 Comorbidity

神经元-胶质细胞机制

基本信息

批准号：
8099498
负责人：
Kurt F Hauser
金额：
$ 12.91万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8099498
关键词：
AIDS Dementia Complex AIDS neuropathy AIDS/HIV problem Acquired Immunodeficiency Syndrome Address Affect Apoptosis Apoptotic Appearance Area Astrocytes Award Brain region Caspase Cause of Death Cessation of life Clinical Coculture Techniques Collaborations Comorbidity Consequences of HIV Corpus striatum structure Drug abuse Epidemic Event Faculty Funding Genetic Vectors Goals Grant HIV HIV Envelope Protein gp120 HIV Infections HIV Seropositivity HIV-1 Health Hepatitis C virus Heroin Heroin Abuse Hippocampus (Brain)Homeostasis Human In Situ Nick-End Labeling In Vitro Independent Scientist Award Individual Infection Injury International Joints Knock-out Mediating Mentors Microglia Molecular Morphine Mus Narcotic Antagonists National Institute of Drug Abuse Nerve Degeneration Neuraxis Neuroglia Neuronal Dysfunction Neurons Neurovirology Nursing Faculty Oligodendroglia Opiates Opioid Opioid Receptor Opium Oxycodone PTEN gene Papaver Pathogenesis Pathologic Pathology Pharmaceutical Preparations Pharmacology and Toxicology Play Principal Investigator Proteins Publishing Recruitment Activity Research Role S-nitro-N-acetylpenicillamine SCID Mice Scientist Self Administration Seminal Signal Pathway Signal Transduction Slice Students Substance abuse problem Synapses Synaptophysin System Testing Therapeutic Intervention Time Toxic effect Training Transfection Transgenic Mice Translational Research Universities Viral Load result Viral Proteins Virginia Virus analog base career caspase-3 density dosage drug abuser drug of abuse endonuclease G humanized SCID mouse in vivo macrophage monocyte mouse model neuroprotection neurotoxic neurotoxicity opioid abuse overexpression pre-doctoral progenitor receptor function responsible research conduct symposium synergism virotoxins

项目摘要

DESCRIPTION (provided by applicant): A K02 independent Scientist Award will enable the candidate to obtain maximum protected time at Virginia Commonwealth University (VCU) to pursue NIDA funded research on substance abuse-HIV-1 comorbidity, acquire advanced cross-disciplinary expertise, and to mentor student and faculty scientists in this area. Drug abuse and HIV-1 are interlinked epidemics with horrific consequences. To address this problem, the candidate directs grant P01 DA19398, "Opiate drug abuse and CNS vulnerability to HIV", is Principal Investigator (PI) on grant R0I DA18633, "Mechanisms of opiate drug-HIV: lnduced neurodegeneration", is a co-l on R01 DA024461, "Glial progenitors as targets of HIV/opiate interactions", is a co-l on a pending NIDA R03 grant to study opioid drug-hepatitis C virus (HCV) interactive pathology, and is a consultant on numerous other projects. The applicant has published seminal studies demonstrating: that opioids can directly affect CNS maturation; the cellular basis of opioid receptor and function in astrocytes and oligodendrocytes; and that opioids intrinsically exacerbate the pathogenesis of neuroAIDS-identifying both intra- and intercellular pathologic mechanisms in neurons and multiple glial types. The applicant has established worldwide collaborations that continue to optimize approaches to opioid abuse-HIV-1 comorbidity, has mentored highly successful pre- and postdoctoral, and basic and clinical faculty; including training in the responsible conduct of research (RCR), has co-directed a NIDA training grant, and organized local and international conferences promoting substance abuse research. A K02 award will enable the candidate to: (1) pursue the goals of current grants, while developing cutting-edge approaches to substance abuse (e.g., self-administration paradigms), HlV-1 (humanized SCID mouse model), and molecular neurovirology; (2) to merge basic and clinical approaches through translational research with the VCU HIV/AIDS Center and joint VCU/Johns Hopkins Univ. NIDA CTN; while continuing to mentor students/early career scientists (including under-represented individuals and an emphasis on RCR). He was recruited to VCU by the Dept. of Pharmacology and Toxicology to pursue these goals and receives tremendous support for this endeavor. PUBLIC HEALTH RELEVANCE: Opioid (heroin) abuse and HIV/AIDS are interrelated epidemics. Not only does drug abuse spread HIV, but also the candidate discovered that opioids intrinsically promote the neurodegenerative effects of HIV. The candidate respectfully requests this award to devote more time to pursue research into the mechanisms underlying opioid drug abuse-HIV interactions to indentify new therapies for opioid abuse and neuroAIDS.

描述（由申请人提供）：K02 独立科学家奖将使候选人能够在弗吉尼亚联邦大学 (VCU) 获得最长的受保护时间，以从事 NIDA 资助的药物滥用-HIV-1 共病研究，获得先进的跨学科专业知识，并指导该领域的学生和教师科学家。药物滥用和 HIV-1 是相互关联的流行病，会带来可怕的后果。为了解决这个问题，候选人指导拨款 P01 DA19398，“阿片类药物滥用和中枢神经系统对艾滋病毒的脆弱性”，是拨款 R0I DA18633 的首席研究员（PI），“阿片类药物 - HIV 的机制：诱发的神经变性”，是一项共同研究l 关于 R01 DA024461，“神经胶质祖细胞作为 HIV/阿片类药物相互作用的目标”，是共同参与一项待决的 NIDA R03 拨款，用于研究阿片类药物与丙型肝炎病毒 (HCV) 相互作用的病理学，并且是许多其他项目的顾问。申请人发表的开创性研究表明：阿片类药物可以直接影响中枢神经系统的成熟；阿片受体的细胞基础及其在星形胶质细胞和少突胶质细胞中的功能；阿片类药物从本质上加剧了神经艾滋病的发病机制——确定了神经元和多种神经胶质类型的细胞内和细胞间病理机制。申请人建立了全球合作，继续优化阿片类药物滥用与 HIV-1 合并症的治疗方法，指导了非常成功的博士前和博士后以及基础和临床教师；包括负责任的研究行为 (RCR) 培训，共同指导 NIDA 培训拨款，并组织促进药物滥用研究的本地和国际会议。 K02 奖将使候选人能够：(1) 追求当前资助的目标，同时开发药物滥用（例如自我管理范式）、HIV-1（人源化 SCID 小鼠模型）和分子神经病毒学的尖端方法; (2) 通过与弗吉尼亚联邦大学艾滋病毒/艾滋病中心和弗吉尼亚联邦大学/约翰霍普金斯大学联合的转化研究，将基础方法和临床方法结合起来。尼达CTN；同时继续指导学生/早期职业科学家（包括代表性不足的个人和对 RCR 的重视）。他被药理学和毒理学系招募到弗吉尼亚联邦大学来追求这些目标，并为此获得了巨大的支持。公共卫生相关性：阿片类药物（海洛因）滥用和艾滋病毒/艾滋病是相互关联的流行病。药物滥用不仅会传播艾滋病毒，而且候选人还发现阿片类药物本质上会促进艾滋病毒的神经退行性影响。候选人恭敬地请求该奖项投入更多时间来研究阿片类药物滥用与艾滋病毒相互作用的机制，以确定阿片类药物滥用和神经艾滋病的新疗法。