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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：
7759260
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/7759260
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 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 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 Urticaria 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 progenitor public health relevance 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）：K 02独立科学家奖将使候选人在弗吉尼亚联邦大学（VCU）获得最大的保护时间，以进行NIDA资助的药物滥用-HIV-1合并症研究，获得先进的跨学科专业知识，并指导学生和教师科学家在这一领域。药物滥用和HIV-1是具有可怕后果的相互关联的流行病。为了解决这一问题，候选人指导资助P01 DA 19398，“阿片类药物滥用和CNS对HIV的脆弱性”，是资助R 0 I DA 18633，“阿片类药物-HIV的机制：诱导的神经变性”，是R 01 DA 024461，“胶质祖细胞作为HIV/阿片相互作用的靶点”，是一个共同的l对一个悬而未决的NIDA R 03赠款研究阿片类药物丙型肝炎病毒（HCV）相互作用的病理学，并在许多其他项目的顾问。申请人已发表了开创性研究，证明：阿片类药物可直接影响CNS成熟;阿片类药物受体的细胞基础和星形胶质细胞和少突胶质细胞中的功能;阿片类药物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细胞类型中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-HIV-1并发症的方法，指导了非常成功的博士前和博士后，基础和临床教师;包括负责任的研究行为（RCR）培训，共同指导了NIDA培训补助金，并组织了促进药物滥用研究的地方和国际会议。K 02奖将使候选人能够：（1）追求目前赠款的目标，同时制定尖端的药物滥用方法（例如，自我管理范例），HIV-1（人源化SCID小鼠模型）和分子神经病毒学;（2）通过与VCU HIV/AIDS中心和VCU/约翰霍普金斯大学联合NIDA CTN的转化研究，合并基础和临床方法;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RCR的重点）。他被部门招募到VCU。药理学和毒理学的追求这些目标，并得到了巨大的支持，这一奋进。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作用。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潜在机制，以确定阿片类药物滥用和神经艾滋病的新疗法。