Deciphering the Link between Severe Acute Respiratory Coronavirus 2 Infection and Long-Term Neurological and Pulmonary Sequelae

解读严重急性呼吸道冠状病毒2感染与长期神经和肺部后遗症之间的联系

基本信息

批准号：
10555082
负责人：
Zea Borok
金额：
$ 115.81万
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：
2022-07-31 至 2024-07-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10555082
关键词：
2019-nCoV ACE2 Address Affect Afferent Neurons Allergens Animal Behavior Anxiety Asthma Award Back Behavioral Brain Brain region Breathing COVID-19 COVID-19 pandemic Cardiovascular system Cell Nucleus Cells Cessation of life Chronic Chronic Disease Chronic Phase Dementia Electrophysiology (science)Ganglia Gene Expression Health Health system Human Hypothalamic structure Impaired cognition In Situ Infection Inflammation Interoception Irritants Lead Link Lung Lung diseases Maps Meditation Mental Depression Mental Health Molecular Molecular Profiling Mus Names National Center for Complementary and Integrative Health Nervous system structure Neuraxis Neurologic Neurologic Symptoms Neurons Organ Parents Pathway interactions Peripheral Physiology Post-Acute Sequelae of SARS-CoV-2 Infection Qi Gong RNA Resolution Respiration Respiratory Tract Infections SARS-CoV-2 infection Scheme Schools Sensory Signal Transduction Spinal Spinal Cord Stress Techniques Technology Testing Thinking Three-Dimensional Imaging Tissues Toxin Viral Work acute infection airway hyperresponsiveness base blood-brain barrier crossing brain fog cell type dorsal motor nucleus epigenomics functional loss gastrointestinal system humanized mouse improved in vivo calcium imaging mouse model neural circuit neurosensory optogenetics paraventricular nucleus parent grant post SARS-CoV-2 infection relating to nervous system response transcriptomics

项目摘要

PROJECT SUMMARY/ABSTRACT Many lung diseases, including asthma, are associated with neurological symptoms such as stress, anxiety and depression. Joining this list is COVID19, where the growing list of post-acute sequelae of SARS-CoV-2 infection (PASC) includes anxiety and depression. Whether and how respiratory infection by SARS-CoV-2 could impact neurological state is not understood. In this supplement, we will continue the theme of the parent award to dissect the functional and neuroanatomical connections between the brain and lung at the molecular and cellular level. We will test the hypothesis that SARS-CoV-2 respiratory infection, acting through chronic changes in lung and the lung-innervating neural circuit, alters neuronal activity and neural inflammation, leading to heightened stress, anxiety and depression. We will use humanized mouse models for SARS-CoV-2 infection to test if respiratory infection alters central nervous system neuronal activity, neural inflammation, gene expression and behavioral changes in the chronic phase of infection (aim 1). We will also use single cell multiome and spatial transcriptomic technologies to define the transcriptomic and epigenomic signature of the human donor lungs in the chronic phase following SARS-CoV-2 infection (aim 2). We anticipate that a comprehensive profile of the brain, the lung, and their connection in the chronic phase of SARS-CoV-2 infection will deepen understanding and inform control of PASC.

项目概要/摘要许多肺部疾病，包括哮喘，都与压力、焦虑等神经系统症状有关和抑郁症。加入此名单的是 COVID19，其中 SARS-CoV-2 的急性后遗症列表不断增加感染（PASC）包括焦虑和抑郁。是否以及如何被 SARS-CoV-2 呼吸道感染是否会影响神经状态尚不清楚。在本次增补中，我们将延续家长的主题该奖项旨在从分子角度剖析大脑和肺之间的功能和神经解剖学联系和细胞水平。我们将检验以下假设：SARS-CoV-2 呼吸道感染通过慢性肺和肺支配神经回路的变化，改变神经元活动和神经炎症，导致压力、焦虑和抑郁加剧。我们将使用 SARS-CoV-2 人源化小鼠模型感染以测试呼吸道感染是否改变中枢神经系统神经元活动、神经炎症、感染慢性期的基因表达和行为变化（目标 1）。我们还将使用单细胞多组和空间转录组技术来定义转录组和表观基因组特征 SARS-CoV-2 感染后慢性期的人类供体肺（目标 2）。我们预计， SARS-CoV-2 慢性期大脑、肺及其连接的全面概况感染将加深对 PASC 的理解并为控制提供信息。