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SARS-CoV-2 promotes...
SARS-CoV-2 promotes microglial synapse elimination in human brain organoids
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, amudyata (author)
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Oliveira, AO (author)
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Malwade, S (author)
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- de Sousa, NR (author)
- Karolinska Institutet
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Goparaju, SK (author)
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Gracias, J (author)
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- Orhan, F (author)
- Karolinska Institutet
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- Steponaviciute, L (author)
- Karolinska Institutet
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- Schalling, M (author)
- Karolinska Institutet
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Sheridan, SD (author)
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Perlis, RH (author)
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- Rothfuchs, AG (author)
- Karolinska Institutet
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- Sellgren, CM (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2022-10-05
- 2022
- English.
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In: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 27:10, s. 3939-3950
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https://doi.org/10.1...
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Abstract
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- Neuropsychiatric manifestations are common in both the acute and post-acute phase of SARS-CoV-2 infection, but the mechanisms of these effects are unknown. In a newly established brain organoid model with innately developing microglia, we demonstrate that SARS-CoV-2 infection initiate neuronal cell death and cause a loss of post-synaptic termini. Despite limited neurotropism and a decelerating viral replication, we observe a threefold increase in microglial engulfment of postsynaptic termini after SARS-CoV-2 exposure. We define the microglial responses to SARS-CoV-2 infection by single cell transcriptomic profiling and observe an upregulation of interferon-responsive genes as well as genes promoting migration and synapse engulfment. To a large extent, SARS-CoV-2 exposed microglia adopt a transcriptomic profile overlapping with neurodegenerative disorders that display an early synapse loss as well as an increased incident risk after a SARS-CoV-2 infection. Our results reveal that brain organoids infected with SARS-CoV-2 display disruption in circuit integrity via microglia-mediated synapse elimination and identifies a potential novel mechanism contributing to cognitive impairments in patients recovering from COVID-19.
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- ref (subject category)
- art (subject category)
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- By the author/editor
-
, amudyata
-
Oliveira, AO
-
Malwade, S
-
de Sousa, NR
-
Goparaju, SK
-
Gracias, J
-
show more...
-
Orhan, F
-
Steponaviciute, ...
-
Schalling, M
-
Sheridan, SD
-
Perlis, RH
-
Rothfuchs, AG
-
Sellgren, CM
-
show less...
- Articles in the publication
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Molecular psychi ...
- By the university
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Karolinska Institutet