Single Cell Transciptomics of the Opioid Use Disorder and HIV Syndemic in the Human Brain

人脑中阿片类药物使用障碍和艾滋病毒综合症的单细胞转录组学

基本信息

批准号：
10699022
负责人：
Christine Cheng
金额：
$ 39.5万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10699022
关键词：
3-Dimensional Acquired Immunodeficiency Syndrome Addictive Behavior Affect Alzheimer&apos s Disease Amygdaloid structure Astrocytes Award Blood Blood - brain barrier anatomy Blood Vessels Brain Brain region Cell Nucleus Cells Chronic Clustered Regularly Interspaced Short Palindromic Repeats Corpus striatum structure Data Set Databases Dementia Development Disease Disease Progression Drug Addiction Drug usage Event Exhibits Exposure to Family Functional disorder Gene Expression Genes HIV HIV Infections HIV-1 HIV-associated neurocognitive disorder Human Immune Immunohistochemistry Immunosuppression In Vitro Incidence Individual Infection Inflammation Inflammatory Knock-out Knowledge Lead Leptomeninges Life Link Microglia Molecular Morphine Neuraxis Neurologic Neuronal Injury Neurons Nucleus Accumbens Opioid Organoids Pathogenesis Pathology Pathway interactions Patients Pattern Persons Pharmaceutical Preparations Phenotype Population Prefrontal Cortex Primary Infection Property Public Health Regulation Route Slice Small Nuclear RNA Social Impacts Substance Use Disorder Technology Testing Tissue-Specific Gene Expression Transcript Tumor-infiltrating immune cells Variant Viral Load result Viral reservoir Work acute infection addiction antiretroviral therapy base blood-brain barrier permeabilization brain cell brain parenchyma brain tissue case control cell type chronic inflammatory disease differential expression economic impact epigenetic regulation gene therapy glial activation immune activation in vivo induced pluripotent stem cell lead candidate neurocognitive disorder neurotoxicity new technology novel opioid misuse opioid use disorder resilience response seroconversion syndemic three dimensional cell culture transcriptome transcriptome sequencing transcriptomics

项目摘要

Blood vessels that vascularize the central nervous system possess unique properties, termed the blood-brain barrier (BBB), which imposes a tight regulation of molecules and cells (particularly immune cells) that move between the blood and the brain. Disrupted BBB may increase immune cell infiltrating into the brain parenchyma and promote glial activation, increased inflammation and neurotoxicity. Interestingly, increased permeability of BBB has been implicated in the progression of Alzheimer's disease. Differential gene expression among cell types, and among individuals likely contributes to selective vulnerability or resilience. This proposal will use single nucleus RNA sequencing to elucidate cell type selective transcriptomes in leptomeninges and associate immune cells from AD and control cases. This work will lead to fundamental advances in our knowledge of cell type specific genes regulating the pathophysiology of neurovasculature and associate immune cell types in AD.

使中枢神经系统血管化的血管具有独特的特性，称为血脑屏障 (BBB)，对分子和细胞进行严格调节（特别是免疫细胞）在血液和大脑之间移动。 BBB 紊乱可能增加免疫细胞浸润脑实质并促进神经胶质活化，增加炎症和神经毒性。有趣的是，BBB 的渗透性增加与阿尔茨海默病的进展有关。细胞间差异基因表达类型以及个体之间的差异可能会导致选择性脆弱性或复原力。这该提案将使用单核 RNA 测序来阐明细胞类型选择性转录组在软脑膜中，并关联来自 AD 和对照病例的免疫细胞。这项工作将导致我们对调节细胞类型特异性基因的认识取得了根本性进展 AD 中神经血管系统的病理生理学和相关免疫细胞类型。