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Single nuclei transcriptome profiling in addiction circuitry of the HIV+ brain

HIV大脑成瘾回路的单核转录组分析

基本信息

批准号：
10783382
负责人：
Schahram Akbarian
金额：
$ 16.86万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10783382
关键词：
Administrative Supplement Affect Anatomy Anterior Area Autopsy Award Biological Assay Brain Brain Stem CD4 Positive T Lymphocytes Cell Nucleus Cells Central Nervous System Diseases Cessation of life Chromatin Chronic Clinical Trials Cocaine Cocaine Abuse Complex Corpus striatum structure DSM-IV Data Set Databases Deposition Diagnosis Diagnostic Disease Documentation Drug abuse Epidemic Exposure to Freezing Funding Funding Opportunities Gene Expression Genes Genetic Fingerprintings Genome Genomics Goals Grant HIV HIV Infections HIV-associated neurocognitive disorder HIV/AIDS High Prevalence Horns Human Individual Interview Libraries Link Microglia Midbrain structure Monitor National Institute of Drug Abuse Neuroanatomy Neurobehavioral Manifestations Neurobiology Neurologic Neurologic Symptoms Neurological status Nuclear Opioid Parents Pathogenesis Peripheral Persons Plasma Positioning Attribute Quality Control Research Site Specimen Structure Structure of genu of corpus callosum Substance Use Disorder Substance abuse problem Syndrome Tissues Toxicology Transcript U-Series Cooperative Agreements United States National Institutes of Health Urine Viral Virus Latency addiction antiretroviral therapy brain cell brain tissue cingulate cortex cingulate gyrus cohort data resource drug of abuse epigenome experimental study high risk human tissue innovation insight neural circuit neuroAIDS neurogenomics novel opioid abuse parent grant parent project programs prospective response single nucleus RNA-sequencing transcriptome transcriptomic profiling transcriptomics white matter

项目摘要

HIV-associated neurocognitive disorders (HAND) persist in the era of combination antiretroviral therapy (cART). HIV latency, and cell-specific expression of HIV transcript in human CNS remains incompletely understood, despite continued high prevalence of HIV-associated neurologic disease and increasing recognition of CNS viral escape in people stably suppressed with cART. Issues of CNS functional deficit are further complicated by the co-registered epidemic of opiate and other substance use disorders (SUD) in people living with HIV/AIDS (PLWHA), as SUD also have profound impact on CNS function, and potentially on HIV latency. Nowhere in the CNS is this more evident than in the neuroanatomic overlap of HIV and SUD in striatonigral dopaminergic circuitry and its cortical projection areas including the anterior cingulate cortex, sites of predilection for functional and neurobiologic disease as well as for increased burden of HIV infection. Accordingly, directly utilizing brain tissues in these regions, from neurologically well-characterized HIV-infected individuals with and without SUD, the goal of this application will be to explore whether HIV signatures in transcriptomes in dopaminergic circuitry i n c l u d i n g c i n g u l a t e t a r g e t s is associated with prospectively monitored neurological status in the years before death and exposure to drug of abuse; (iii) explore HIV expression in potential reservoir cells of the brain, including microglia. The innovative experiments proposed here are expected to offer novel insights into transcriptomic landscapes in specific brain cells and explore potential links between neurogenomic status of the infected brain and neurological and cognitive symptoms and substance abuse. While recognizing the high-risk aspects, these analyses will nevertheless have predictable, high gain benefits in understanding the complex neurobiology underlying HIV-associated CNS disease in PLWHA and SUD.

hiv相关神经认知障碍（HAND）在联合抗逆转录病毒时代持续存在