Cited by 75Long-Term Effects of COVID-19Mitochondrial Function and PathologyNeuroinflammation and Neurodegeneration Mechanisms

Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID

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Clough, Erin, Inigo, Joseph, Chandra, Dhyan, Chaves, Lee, Reynolds, Jessica L., Aalinkeel, Ravikumar, Schwartz, Stanley A., Khmaladze, Alexander +1 more·2021·Journal of Neuroimmune Pharmacology

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.

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  • SARS-CoV-2 RNA has been detected in EVs.

    “This is also true for SARS-CoV-2 RNA, which has been detected in EVs.”

    From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [48]

    The RNA Extraction and Real Time qPCR sections describe RNA taken from microglial cells, not extracellular vesicles. Searches for extracellular vesicles, EVs, exosomes, and viral RNA found no passage reporting SARS-CoV-2 RNA in EVs. (LLM, conf=0.76)

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Authors
Clough, E., Inigo, J., Chandra, D., Chaves, L., Reynolds, J. L., Aalinkeel, R., Schwartz, S. A., Khmaladze, A., & Mahajan, S. D.
Affiliations
  • University at Buffalo, State University of New York (US)
  • Roswell Park Comprehensive Cancer Center (US)
  • University at Albany, State University of New York (US)
Corresponding author
Mahajan, Supriya D.
Venue
Journal of Neuroimmune Pharmacology
Published
2021-10-02
Volume
16
Issue
4
Pages
770-784
ISSN
  • 1557-1890 (ISSN-L)
  • 1557-1904
OpenAlex
W3203893617
Cited by
75
References
74
Citations by year
2026: 6 · 2025: 10 · 2024: 19 · 2023: 21 · 2022: 18 · 2021: 1
FWCI
7.06
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroimmune Pharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (USA-WA1/2020, HHSN272201400008C, NR-52286)
  • National Institute on Drug Abuse (R01DA047410)
  • National Institute of Allergy and Infectious Diseases (HHSN272201400008C), USA-WA1/2020, R01AI129649)
Topics
  • Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
SARS-CoV-2 spike protein, neuro-COVID, microglia, mitochondrial dysfunction, mitochondrial biogenesis, apoptosis, reactive oxygen species, oxidative stress, oxygen consumption rate, inflammatory cytokines, phospholipid composition, mitochondrial membrane lipids, Raman spectroscopy, neuroinflammation, neuronal injury
MeSH terms
COVID-19, SARS-CoV-2, Humans, RNA, Viral, Microglia, Pandemics, Mitochondrial Dynamics, Spike Glycoprotein, Coronavirus

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