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Assessment of fetal brain health via circulating exRNA carriers for opioid use disorder in pregnancy

通过循环 exRNA 载体评估妊娠期阿片类药物使用障碍的胎儿大脑健康

基本信息

批准号：
10722040
负责人：
Daniel T Chiu
金额：
$ 71.81万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10722040
关键词：
Address Affinity Biological Biological Assay Biological Markers Birth Blood Brain Brain Diseases Cells Central Nervous System Centrifugation Complex Detection Development Dose Dyes Enzyme-Linked Immunosorbent Assay Exclusion Exposure to Flow Cytometry Fluorescence Fluorescence-Activated Cell Sorting Genetic Glycoproteins Growth HIV Infections Health Heterogeneity In Situ Individual Infant Membrane Proteins Methodology Methods Molecular Mothers Neonatal Abstinence Syndrome Newborn Infant Nucleic Acids Opioid Outcome Pathologic Pathway interactions Penetration Peptides Pharmaceutical Preparations Pharmacotherapy Phenotype Physiological Plasma Polymers Population Precipitation Predisposition Pregnancy Pregnancy Complications Pregnant Women Process Proteins Public Health RNA Reporting Reverse Transcriptase Polymerase Chain Reaction Risk Risk Assessment Sampling Second Pregnancy Trimester Seizures Severities Signal Transduction Sorting Stains Substance Use Disorder Surface Surveys Synaptophysin Systems Analysis Techniques Technology Third Pregnancy Trimester Treatment Cost United States Western Blotting Woman Work brain health candidate identification cognitive function contactin experience extracellular extracellular vesicles fetal fetal brain injury fluorophore healthy pregnancy in utero insight maternal opioid use neonate neurodevelopment new technology non-drug opioid epidemic opioid exposure opioid therapy opioid use opioid use disorder particle response tool

项目摘要

Project Summary We are submitting this proposal in response to PAR-20-147 (Extracellular RNA carrier subclasses in processes relevant to Substance Use Disorders or HIV infection). The opioid epidemic in the United States has far reaching consequences for public health. In recent decades, the rate of newborns born with neonatal abstinence syndrome (NAS) has increased dramatically. However, not all neonates exposed to opioids during gestation develop NAS or require treatment. NAS is a complex and idiosyncratic condition, and it is currently not possible to predict even at birth which infants will require pharmacotherapy or be susceptible to its worst outcomes. Accessible biomarkers for fetal brain and CNS development during opioid exposure would be highly valuable for deciding which infants will need opioid therapy for NAS and making personalized risk assessments for opioid exposed infants. They could also shed light on the biological pathways that lead to the worst effects of opioid exposure during gestation. Extracellular vesicles (EVs) derived from the Fetal brain and central Nervous system (FNEV) can cross the fetal/placental barrier and can be isolated from maternal blood. They represent a powerful accessible tool to provide insight on fetal neurodevelopment and damage. However, EVs are highly heterogeneous, with a diverse set of surface proteins and intra-vesicular cargo, such as RNA. Current approaches to the isolation and study of EVs lack the necessary sensitivity and precision to characterize EV subpopulations. To address the current limitations of EV analyses, we developed a high-throughput single-EV flow analyzer and sorter capable of detecting single dye molecules. This new technical capability allows us to exquisitely define the profiles of plasma FNEV during pregnancy. Our studies could lead to assays that define NAS risk pre-birth and bring new insights into the mechanistic pathways of fetal brain injury.

项目总结