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Center for Integrative Neuroscience

综合神经科学中心

基本信息

批准号：
10853703
负责人：
MICHAEL A WEBSTER
金额：
$ 35.81万
依托单位：
UNIVERSITY OF NEVADA RENO
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：
2022-07-15 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10853703
关键词：
ACE2 Acute Anosmia Anxiety Area Artificial Intelligence Binding Biological Markers Biology Blood Brain COVID-19 patient Caenorhabditis elegans Centers of Research Excellence Chronic Fatigue Syndrome Clinical Cognitive Collaborations Complex Core Facility Data Data Analyses Data Analytics Development Diabetes Mellitus Diagnosis Disease Drosophila genus Drowsiness Fatigue Functional Magnetic Resonance Imaging Funding Funding Opportunities Future Genes Goals Human Impaired cognition Individual Infection Inflammatory Infrastructure Insulin Insulin Resistance Interdisciplinary Study Knock-out Kynurenine Link Long COVID Measures Medical center Mental Depression Modeling Modernization Molecular Neurobiology Neurologic Neurologic Symptoms Neurosciences Neurosciences Research Nevada Non-Insulin-Dependent Diabetes Mellitus Outcome Pathogenesis Pathway interactions Patients Phase Pilot Projects Play Post-Acute Sequelae of SARS-CoV-2 Infection Prognosis Psychology RNA Viruses Research Research Personnel Rest Role SARS-CoV-2 infection Serum Proteins Services Signal Transduction Signaling Molecule Sleep Sleep disturbances Smell Perception Specimen Symptoms Taste Perception Testing Tilia Training Viral Virus Virus Diseases Vision accurate diagnosis biomarker identification cellular imaging coronavirus disease cytokine deep learning diabetic diagnostic biomarker disabling symptom experimental study follow-up gamma-Aminobutyric Acid insight insulin signaling longitudinal analysis medical schools model organism molecular imaging multidisciplinary neural neuroimaging neuropathology novel olfactory sensory neurons post SARS-CoV-2 infection protein biomarkers recruit response skills symptom management synergism tool training opportunity transmission process

项目摘要

PROJECT SUMMARY (supplement) The long-term goal of this project is to understand the mechanisms underlying the pathogenesis and neural symptoms of long-COVID/PASC, including cognitive impairments, fatigue, and loss of smell. Distinct mechanisms may be at play due to multiple potentially overlapping causes of long-COVID. There is thus an urgent need to merge diverse perspectives and approaches to study long-COVID’s pathogenesis and neural symptoms. The short-term goal of this pilot study is to establish a research framework and strengthen a collaboration of investigators with diverse backgrounds and skill sets to mount a truly multidisciplinary proposal to understand the neuropathology of long-COVID. Toward this goal, aim 1 of this project will leverage the C. elegans model organism to understand the role of the inflammatory kynurenine pathway (KP) and its neuroactive metabolites in viral infection-induced sleepiness/fatigue. Aim 2 will use the Drosophila olfactory sensory neurons as a model to study the molecular interactions between the Covid-ACE2 (viral) and insulin (diabetic) pathways and their relationship to smell loss. Aim 3 will use human patients diagnosed with long-COVID to assess changes in brain network topology. Aim 4 will use human specimens to investigate serum protein biomarkers by performing longitudinal analysis of specific inflammatory biomarkers (e.g., cytokines, kynurenine, etc.) early following COVID-19 infection and in those that develop long-COVID. The results will shed light on candidate inflammatory biomarkers such as cytokines, kynurenine, and changes in brain connectivity in patients with long- COVID symptoms. They could lead to a more accurate diagnosis and prognosis of long-COVID. Finally, the results will help us reinforce this unique collaboration and optimize future directions to study long-COVID mechanisms. Our proposal synergizes well with the broader goals of the Integrative Neuroscience COBRE at UNR, which aims to synergize and elevate neuroscience research capacity at UNR and across Nevada. First, this unique multidisciplinary collaboration fulfills the central goal of the COBRE to cross-fertilize research units that have already developed expertise in cognitive and cellular neuroscience. Second, by extensively using core facilities, such as the Neuroimaging, and Cellular and Molecular Imaging cores, the project takes advantage of the modern infrastructure established at UNR and Renown Medical Center by COBRE Phases I and II to mount impactful research in neuroscience. Third, our extensive use of computational analytics and the incorporation of artificial intelligence in our data analysis plans align with the future vision of Phase III of COBRE, which is to expand data analytics service to include AI and deep learning facilities. Lastly, this project combines diverse approaches and perspectives to tackle important questions about neurological long-COVID, which will lead to unique collaborative research and training opportunities in the future, further advancing COBRE’s goals to build research capacity at UNR and new funding opportunities in neuroscience.

项目总结(补编) 这个项目的长期目标是了解发病机制和神经机制。慢性COVID/PASC的症状，包括认知障碍、疲劳和嗅觉丧失。截然不同由于多种可能重叠的长期冠状病毒感染原因，机制可能正在发挥作用。因此，有一种迫切需要融合不同的视角和方法来研究长冠状病毒的发病机制和神经症状。这项试点研究的短期目标是建立一个研究框架，并加强具有不同背景和技能的调查人员协作，提出真正的多学科提案了解慢性冠状病毒感染的神经病理。为了实现这一目标，本项目的目标1将利用C. 线虫模型生物了解炎性犬尿氨酸途径(KP)的作用及其神经活性病毒感染引起嗜睡/疲劳的代谢物。目标2将使用果蝇嗅觉神经元作为研究Covid-ACE2(病毒)和胰岛素(糖尿病)途径之间分子相互作用的模型以及它们与嗅觉丧失的关系。AIM 3将使用被诊断为长期冠状病毒感染的人类患者来评估变化在大脑网络拓扑中。Aim 4将使用人类样本通过以下方式研究血清蛋白质生物标记物对特定的炎症生物标志物(如细胞因子、犬尿氨酸等)进行纵向分析早些时候在新冠肺炎感染后和那些发展为长期冠状病毒感染者。选举结果将为候选人提供线索炎性生物标志物，如细胞因子、犬尿氨酸和脑连接性的改变冠状病毒症状。它们可能导致更准确的诊断和预后的长期COVID。最后，研究结果将帮助我们加强这一独特的合作，并优化未来研究Long-CoVID的方向机制。我们的建议与综合神经科学中心的更广泛目标很好地协同在 UNR，旨在协同和提高UNR和整个内华达州的神经科学研究能力。第一, 这种独特的多学科合作实现了科布雷交叉培养研究单位的中心目标他们已经在认知和细胞神经科学方面发展出专业知识。第二，通过广泛使用核心设施，如神经成像，以及细胞和分子成像核心，该项目利用科布雷一期和二期在UNR和名镇医疗中心建立的现代化基础设施将安装神经科学领域有影响力的研究。第三，我们对计算分析的广泛使用和对我们数据分析计划中的人工智能与Cobre第三阶段的未来愿景保持一致，即扩展数据分析服务，将人工智能和深度学习设施包括在内。最后，这个项目结合了不同的解决有关神经系统长期冠状病毒感染的重要问题的方法和观点，这将导致未来独特的协作研究和培训机会，进一步推进Cobre的建设目标 UNR的研究能力和神经科学方面的新资金机会。