Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV
肠道微生物组-脑轴在阿片类药物暴露和 HIV 产生的神经病理学中调节中枢神经系统炎症小体的作用
基本信息
- 批准号:10653501
- 负责人:
- 金额:$ 15.35万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-30 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:Acquired Immunodeficiency SyndromeAnimalsAntibioticsAttentionAttenuatedBacterial TranslocationBindingBiologicalBrainBreedingCellsChronicComplexDataDevelopmentDiseaseDisease ProgressionDrug abuseDrug usageDrug userEndotoxinsEnterococcus faecalisExtravasationFirmicutesFunctional disorderGenesGerm-FreeGram-Negative BacteriaGram-Positive BacteriaHIVHIV Envelope Protein gp120HIV InfectionsHIV-1ImmuneImmune systemIndividualInfectionInflammasomeInflammationInflammation MediatorsInflammatoryInflammatory ResponseLeadLeaky GutLigandsLoxP-flanked alleleMicrogliaModelingMolecularMorphineMusNeurocognitiveNeuropathogenesisOpiate AddictionOpioidPatientsPatternPredispositionPrevalenceProbioticsProductionProteinsRibosomesRodent ModelRoleSignal PathwaySignal TransductionTLR2 geneTestingTissuesToll-like receptorsantagonistbacterial communitycytokinedrug abuserdysbiosisgut microbiomegut microbiotamarenostrinmicrobialmicrobial compositionmicrobiotaneurocognitive disorderneuroinflammationneuropathologyopioid abuseopioid exposureopioid usepathogenreceptorsexsubstance usesystemic inflammatory response
项目摘要
Project Summary
Infection with Covid-19 has reached pandemic status with more than 125 million confirmed cases and 2.75
million deaths making it one of the most deadliest pandemics in history. It is associated with severe acute
respiratory syndrome symptoms with high fatality rates. SARS-CoV-2 infection is initiated when its S-protein
binds to the angiotensin-converting enzyme 2 (ACE2) receptor through which it gains entry into the host's cells
(Kuba et al., 2005; Walls et al., 2020). ACE2 is highly expressed in the in the lungs and to a lesser degree in
other organs, such as the heart, kidneys, and intestines (Bavishi et al., 2020), which explains the increased
prevalence of lung infection. An analysis of electronic health record data from more than 73 million patients
showed that people with SUDs are at higher risk of contracting and suffering worse consequences from COVID-
19 particularly among African Americans. Those with an opioid use disorder (OUD) were 2.4 times more likely
to have COVID-19 than those with cocaine use disorder (1.6 times), alcohol use disorder (1.4 times), and
tobacco use disorder (smoking or vaping; 1.3 times). Our recent preliminary data show that chronic opioid
treatment in a mouse model of opioid substance abuse resulted in significant increase in the expression ACE2
expression in the lungs and brain of these animals. This data suggests that long term exposure to opioids by
increasing ACE2 expression in the lung will increase the susceptibility to COVID 19 infection and its expression
in the brain suggests high likely hood of neuro-invasiveness. In this supplement we will test the hypothesis that
substance use disorders with opioids will increase the risk for COVID 19 infection in the lung and will be
associated with neuropathological consequence as a consequence of increased ACE2 expression in brain cells.
In Aim 1: We will investigate the expression of ACE2 in small intestine, lung and brain cells in both male and
female mice that are chronically treated with morphine. We will further investigate if substance abuse in context
of HIV further exacerbates infection and disease progression. In Aim 2; we will investigate using a humanized
mouse model where the murine ACE2 receptor is knocked in, the infectivity of the SARS-CoV2 Spike Protein-
Pseudotyped GFP using both in vitro and in vivo target cells. In Aim 3 we will investigate the role of the gut
microbiome in modulating ACE2 expression levels in the small intestine, lung and brain.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Sabita Roy其他文献
Sabita Roy的其他文献
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{{ truncateString('Sabita Roy', 18)}}的其他基金
(PQ6) Mesenchymal stem cell based and immunocompetent mouse models of HIV/AIDS KSHV-driven sarcomagenesis
(PQ6) 基于间充质干细胞和免疫活性的 HIV/AIDS 小鼠模型 KSHV 驱动的肉瘤发生
- 批准号:
10388236 - 财政年份:2021
- 资助金额:
$ 15.35万 - 项目类别:
(PQ6) Mesenchymal stem cell based and immunocompetent mouse models of HIV/AIDS KSHV-driven sarcomagenesis
(PQ6) 基于间充质干细胞和免疫活性的 HIV/AIDS 小鼠模型 KSHV 驱动的肉瘤发生
- 批准号:
10609000 - 财政年份:2021
- 资助金额:
$ 15.35万 - 项目类别:
Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV
肠道微生物组-脑轴在阿片类药物暴露和 HIV 产生的神经病理学中调节中枢神经系统炎症小体的作用
- 批准号:
10434855 - 财政年份:2019
- 资助金额:
$ 15.35万 - 项目类别:
Multidisciplinary Training in Substance Abuse Research
药物滥用研究的多学科培训
- 批准号:
10395444 - 财政年份:2019
- 资助金额:
$ 15.35万 - 项目类别:
Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV
肠道微生物组-脑轴在阿片类药物暴露和 HIV 产生的神经病理学中调节中枢神经系统炎症小体的作用
- 批准号:
10434466 - 财政年份:2019
- 资助金额:
$ 15.35万 - 项目类别:
Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV
肠道微生物组-脑轴在阿片类药物暴露和 HIV 产生的神经病理学中调节中枢神经系统炎症小体的作用
- 批准号:
10518777 - 财政年份:2019
- 资助金额:
$ 15.35万 - 项目类别:
Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV
肠道微生物组-脑轴在阿片类药物暴露和 HIV 产生的神经病理学中调节中枢神经系统炎症小体的作用
- 批准号:
10754697 - 财政年份:2019
- 资助金额:
$ 15.35万 - 项目类别:
Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV
肠道微生物组-脑轴在阿片类药物暴露和 HIV 产生的神经病理学中调节中枢神经系统炎症小体的作用
- 批准号:
10197088 - 财政年份:2019
- 资助金额:
$ 15.35万 - 项目类别:
Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV
肠道微生物组-脑轴在阿片类药物暴露和 HIV 产生的神经病理学中调节中枢神经系统炎症小体的作用
- 批准号:
10020183 - 财政年份:2019
- 资助金额:
$ 15.35万 - 项目类别:
Multidisciplinary Training in Substance Abuse Research
药物滥用研究的多学科培训
- 批准号:
9919533 - 财政年份:2019
- 资助金额:
$ 15.35万 - 项目类别:
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