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Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID
ABSTRACT: Emerging clinical data from the current COVID-19 pandemic suggests that ~ 40% of COVID-19 patients develop neurological symptoms attributed to viral encephalitis while in COVID long haulers chronic neuro-inflammation and neuronal damage result in a syndrome described as Neuro-COVID. We hyp...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487226/ https://www.ncbi.nlm.nih.gov/pubmed/34599743 http://dx.doi.org/10.1007/s11481-021-10015-6 |
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author | Clough, Erin Inigo, Joseph Chandra, Dhyan Chaves, Lee Reynolds, Jessica L. Aalinkeel, Ravikumar Schwartz, Stanley A. Khmaladze, Alexander Mahajan, Supriya D. |
author_facet | Clough, Erin Inigo, Joseph Chandra, Dhyan Chaves, Lee Reynolds, Jessica L. Aalinkeel, Ravikumar Schwartz, Stanley A. Khmaladze, Alexander Mahajan, Supriya D. |
author_sort | Clough, Erin |
collection | PubMed |
description | ABSTRACT: Emerging clinical data from the current COVID-19 pandemic suggests that ~ 40% of COVID-19 patients develop neurological symptoms attributed to viral encephalitis while in COVID long haulers chronic neuro-inflammation and neuronal damage result in a syndrome described as Neuro-COVID. We hypothesize that SAR-COV2 induces mitochondrial dysfunction and activation of the mitochondrial-dependent intrinsic apoptotic pathway, resulting in microglial and neuronal apoptosis. The goal of our study was to determine the effect of SARS-COV2 on mitochondrial biogenesis and to monitor cell apoptosis in human microglia non-invasively in real time using Raman spectroscopy, providing a unique spatio-temporal information on mitochondrial function in live cells. We treated human microglia with SARS-COV2 spike protein and examined the levels of cytokines and reactive oxygen species (ROS) production, determined the effect of SARS-COV2 on mitochondrial biogenesis and examined the changes in molecular composition of phospholipids. Our results show that SARS- COV2 spike protein increases the levels of pro-inflammatory cytokines and ROS production, increases apoptosis and increases the oxygen consumption rate (OCR) in microglial cells. Increases in OCR are indicative of increased ROS production and oxidative stress suggesting that SARS-COV2 induced cell death. Raman spectroscopy yielded significant differences in phospholipids such as Phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC), which account for ~ 80% of mitochondrial membrane lipids between SARS-COV2 treated and untreated microglial cells. These data provide important mechanistic insights into SARS-COV2 induced mitochondrial dysfunction which underlies neuropathology associated with Neuro-COVID. GRAPHICAL ABSTRACT: [Image: see text] |
format | Online Article Text |
id | pubmed-8487226 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-84872262021-10-04 Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID Clough, Erin Inigo, Joseph Chandra, Dhyan Chaves, Lee Reynolds, Jessica L. Aalinkeel, Ravikumar Schwartz, Stanley A. Khmaladze, Alexander Mahajan, Supriya D. J Neuroimmune Pharmacol Original Article ABSTRACT: Emerging clinical data from the current COVID-19 pandemic suggests that ~ 40% of COVID-19 patients develop neurological symptoms attributed to viral encephalitis while in COVID long haulers chronic neuro-inflammation and neuronal damage result in a syndrome described as Neuro-COVID. We hypothesize that SAR-COV2 induces mitochondrial dysfunction and activation of the mitochondrial-dependent intrinsic apoptotic pathway, resulting in microglial and neuronal apoptosis. The goal of our study was to determine the effect of SARS-COV2 on mitochondrial biogenesis and to monitor cell apoptosis in human microglia non-invasively in real time using Raman spectroscopy, providing a unique spatio-temporal information on mitochondrial function in live cells. We treated human microglia with SARS-COV2 spike protein and examined the levels of cytokines and reactive oxygen species (ROS) production, determined the effect of SARS-COV2 on mitochondrial biogenesis and examined the changes in molecular composition of phospholipids. Our results show that SARS- COV2 spike protein increases the levels of pro-inflammatory cytokines and ROS production, increases apoptosis and increases the oxygen consumption rate (OCR) in microglial cells. Increases in OCR are indicative of increased ROS production and oxidative stress suggesting that SARS-COV2 induced cell death. Raman spectroscopy yielded significant differences in phospholipids such as Phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC), which account for ~ 80% of mitochondrial membrane lipids between SARS-COV2 treated and untreated microglial cells. These data provide important mechanistic insights into SARS-COV2 induced mitochondrial dysfunction which underlies neuropathology associated with Neuro-COVID. GRAPHICAL ABSTRACT: [Image: see text] Springer US 2021-10-02 2021 /pmc/articles/PMC8487226/ /pubmed/34599743 http://dx.doi.org/10.1007/s11481-021-10015-6 Text en © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021, corrected publication 2021 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Original Article Clough, Erin Inigo, Joseph Chandra, Dhyan Chaves, Lee Reynolds, Jessica L. Aalinkeel, Ravikumar Schwartz, Stanley A. Khmaladze, Alexander Mahajan, Supriya D. Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID |
title | Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID |
title_full | Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID |
title_fullStr | Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID |
title_full_unstemmed | Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID |
title_short | Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID |
title_sort | mitochondrial dynamics in sars-cov2 spike protein treated human microglia: implications for neuro-covid |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487226/ https://www.ncbi.nlm.nih.gov/pubmed/34599743 http://dx.doi.org/10.1007/s11481-021-10015-6 |
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