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

被引:0
作者
Salvador, Melanie [1 ]
Tseng, Noah [1 ]
Park, Camdon [1 ]
Williams, Grace [1 ]
Vethan, Arianne [1 ]
Thomas, Grant [1 ]
Baker, John [1 ]
Hemry, Joseph [1 ]
Hammond, Emma [1 ]
Freeburg, Paige [1 ]
Chou, Guan-Wen [2 ]
Taylor, Nick [1 ]
Lu, Yi-Fan [1 ,3 ]
机构
[1] Westmont Coll, Biol Dept, Santa Barbara, CA USA
[2] North Carolina State Univ, Dept Comp Sci, Chapel Hill, NC USA
[3] 955 La Paz Rd, Santa Barbara, CA 93108 USA
来源
ANNALS OF MEDICINE AND SURGERY | 2023年 / 85卷 / 07期
关键词
SARS-CoV-2; spike protein; micro-electrode arrays; neuronal bursts; receptor binding domain;
D O I
10.1097/MS9.0000000000000950
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: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.
引用
收藏
页码:3469 / 3476
页数:8
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