Brain exposure to SARS-CoV-2 virions perturbs synaptic homeostasis.

Brain exposure to SARS-CoV-2 virions perturbs synaptic homeostasis.

Publication date: Mar 28, 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with short- and long-term neurological complications. The variety of symptoms makes it difficult to unravel molecular mechanisms underlying neurological sequalae after coronavirus disease 2019 (COVID-19). Here we show that SARS-CoV-2 triggers the up-regulation of synaptic components and perturbs local electrical field potential. Using cerebral organoids, organotypic culture of human brain explants from individuals without COVID-19 and post-mortem brain samples from individuals with COVID-19, we find that neural cells are permissive to SARS-CoV-2 to a low extent. SARS-CoV-2 induces aberrant presynaptic morphology and increases expression of the synaptic components Bassoon, latrophilin-3 (LPHN3) and fibronectin leucine-rich transmembrane protein-3 (FLRT3). Furthermore, we find that LPHN3-agonist treatment with Stachel partially restored organoid electrical activity and reverted SARS-CoV-2-induced aberrant presynaptic morphology. Finally, we observe accumulation of relatively static virions at LPHN3-FLRT3 synapses, suggesting that local hindrance can contribute to synaptic perturbations. Together, our study provides molecular insights into SARS-CoV-2-brain interactions, which may contribute to COVID-19-related neurological disorders.

Concepts Keywords
Agonist Brain
Bassoon Coronavirus
Coronavirus Cov
Homeostasis Covid
Rich Electrical
Find
Individuals
Local
Lphn3
Molecular
Neurological
Perturbs
Sars
Synaptic
Virions

Semantics

Type Source Name
disease VO Severe acute respiratory syndrome coronavirus 2
disease MESH infection
disease MESH complications
disease MESH coronavirus disease 2019
drug DRUGBANK L-Leucine
disease MESH neurological disorders

Original Article

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