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SARS-CoV-2 spike protein reduces burst activities in neurons measured by micro-electrode arrays

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) caused a large-scale global pandemic between 2020 and 2022. Despite efforts to understand its biological and pathogenic mechanisms, the viral impact on the neurological systems remains unclear. The main goal of this study was to quantify t...

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Autores principales: Salvador, Melanie, Tseng, Noah, Park, Camdon, Williams, Grace, Vethan, Arianne, Thomas, Grant, Baker, John, Hemry, Joseph, Hammond, Emma, Freeburg, Paige, Chou, Guan-Wen, Taylor, Nick, Lu, Yi-Fan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10328704/
https://www.ncbi.nlm.nih.gov/pubmed/37427167
http://dx.doi.org/10.1097/MS9.0000000000000950
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author Salvador, Melanie
Tseng, Noah
Park, Camdon
Williams, Grace
Vethan, Arianne
Thomas, Grant
Baker, John
Hemry, Joseph
Hammond, Emma
Freeburg, Paige
Chou, Guan-Wen
Taylor, Nick
Lu, Yi-Fan
author_facet Salvador, Melanie
Tseng, Noah
Park, Camdon
Williams, Grace
Vethan, Arianne
Thomas, Grant
Baker, John
Hemry, Joseph
Hammond, Emma
Freeburg, Paige
Chou, Guan-Wen
Taylor, Nick
Lu, Yi-Fan
author_sort Salvador, Melanie
collection PubMed
description Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) caused a large-scale global pandemic between 2020 and 2022. Despite efforts to understand its biological and pathogenic mechanisms, the viral impact on the neurological systems remains unclear. The main goal of this study was to quantify the neurological phenotypes induced by the SARS-CoV-2 spike protein in neurons, as measured by in-vitro multiwell micro-electrode arrays (MEAs). MATERIALS AND METHODS: The authors extracted the whole-brain neurons from the newborn P1 mice and plated them on multiwell MEAs and administered purified recombinant spike proteins (both S1 and S2 subunits) from the SARS-CoV-2 virus. The signals from the MEAs were transmitted from an amplifier to a high-performance computer for recording and analysis using an in-house developed algorithm to quantify neuronal phenotypes. RESULTS: Primary among the phenotypic features analyzed, we discovered that neuronal treatment with spike 1 protein (S1) protein from SARS-CoV-2 decreased the mean burst numbers observed on each electrode, an effect that could be rescued with an anti-S1 antibody. Conversely, this mean burst number decrease was not observed with spike 2 protein (S2) treatment. Finally, our data strongly suggest that the receptor binding domain of S1 is responsible for the reduction in neuronal burst activity. CONCLUSION: Overall, our results strongly indicate that spike proteins may play an important role in altering neuronal phenotypes, specifically the burst patterns, when neurons are exposed during early development.
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spelling pubmed-103287042023-07-08 SARS-CoV-2 spike protein reduces burst activities in neurons measured by micro-electrode arrays Salvador, Melanie Tseng, Noah Park, Camdon Williams, Grace Vethan, Arianne Thomas, Grant Baker, John Hemry, Joseph Hammond, Emma Freeburg, Paige Chou, Guan-Wen Taylor, Nick Lu, Yi-Fan Ann Med Surg (Lond) Original Research Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) caused a large-scale global pandemic between 2020 and 2022. Despite efforts to understand its biological and pathogenic mechanisms, the viral impact on the neurological systems remains unclear. The main goal of this study was to quantify the neurological phenotypes induced by the SARS-CoV-2 spike protein in neurons, as measured by in-vitro multiwell micro-electrode arrays (MEAs). MATERIALS AND METHODS: The authors extracted the whole-brain neurons from the newborn P1 mice and plated them on multiwell MEAs and administered purified recombinant spike proteins (both S1 and S2 subunits) from the SARS-CoV-2 virus. The signals from the MEAs were transmitted from an amplifier to a high-performance computer for recording and analysis using an in-house developed algorithm to quantify neuronal phenotypes. RESULTS: Primary among the phenotypic features analyzed, we discovered that neuronal treatment with spike 1 protein (S1) protein from SARS-CoV-2 decreased the mean burst numbers observed on each electrode, an effect that could be rescued with an anti-S1 antibody. Conversely, this mean burst number decrease was not observed with spike 2 protein (S2) treatment. Finally, our data strongly suggest that the receptor binding domain of S1 is responsible for the reduction in neuronal burst activity. CONCLUSION: Overall, our results strongly indicate that spike proteins may play an important role in altering neuronal phenotypes, specifically the burst patterns, when neurons are exposed during early development. Lippincott Williams & Wilkins 2023-06-10 /pmc/articles/PMC10328704/ /pubmed/37427167 http://dx.doi.org/10.1097/MS9.0000000000000950 Text en Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (https://creativecommons.org/licenses/by/4.0/) (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/)
spellingShingle Original Research
Salvador, Melanie
Tseng, Noah
Park, Camdon
Williams, Grace
Vethan, Arianne
Thomas, Grant
Baker, John
Hemry, Joseph
Hammond, Emma
Freeburg, Paige
Chou, Guan-Wen
Taylor, Nick
Lu, Yi-Fan
SARS-CoV-2 spike protein reduces burst activities in neurons measured by micro-electrode arrays
title SARS-CoV-2 spike protein reduces burst activities in neurons measured by micro-electrode arrays
title_full SARS-CoV-2 spike protein reduces burst activities in neurons measured by micro-electrode arrays
title_fullStr SARS-CoV-2 spike protein reduces burst activities in neurons measured by micro-electrode arrays
title_full_unstemmed SARS-CoV-2 spike protein reduces burst activities in neurons measured by micro-electrode arrays
title_short SARS-CoV-2 spike protein reduces burst activities in neurons measured by micro-electrode arrays
title_sort sars-cov-2 spike protein reduces burst activities in neurons measured by micro-electrode arrays
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10328704/
https://www.ncbi.nlm.nih.gov/pubmed/37427167
http://dx.doi.org/10.1097/MS9.0000000000000950
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