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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.

项目总结/摘要许多肺部疾病，包括哮喘，都与神经系统症状有关，如压力，焦虑，和抑郁症加入这一名单的是COVID 19，其中SARS-CoV-2急性后后遗症的名单越来越多感染（PASC）包括焦虑和抑郁。呼吸道感染是否以及如何被SARS-CoV-2感染可能会影响神经系统的状态。在这篇增刊中，我们将继续讨论家长的主题。该奖项旨在从分子水平上解剖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，导致压力加剧焦虑和抑郁我们将使用SARS-CoV-2的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（目的1）。我们还将使用单细胞多基因组和空间转录组技术，以确定转录组和表观基因组的签名， SARS-CoV-2感染后慢性期的人类供体肺（目的2）。我们预计， SARS-CoV-2慢性期脑、肺及其连接的综合概况感染将加深对PASC了解并提供控制信息。