tetano
Editor, Senior Moderator
Nat Microbiol
. 2024 Mar 28.
doi: 10.1038/s41564-024-01657-2. Online ahead of print. Brain exposure to SARS-CoV-2 virions perturbs synaptic homeostasis
Emma Partiot[SUP] 1 2 [/SUP], Aurélie Hirschler[SUP] 3 4 [/SUP], Sophie Colomb[SUP] 5 6 [/SUP], Willy Lutz[SUP] 1 2 7 [/SUP], Tine Claeys[SUP] 8 9 [/SUP], François Delalande[SUP] 3 4 [/SUP], Maika S Deffieu[SUP] 1 2 [/SUP], Yonis Bare[SUP] 1 2 [/SUP], Judith R E Roels[SUP] 10 [/SUP], Barbara Gorda[SUP] 1 2 [/SUP], Joanna Bons[SUP] 3 4 [/SUP], Domitille Callon[SUP] 11 12 [/SUP], Laurent Andreoletti[SUP] 11 12 [/SUP], Marc Labrousse[SUP] 12 13 [/SUP], Frank M J Jacobs[SUP] 10 [/SUP], Valérie Rigau[SUP] 2 14 [/SUP], Benoit Charlot[SUP] 2 15 [/SUP], Lennart Martens[SUP] 8 9 [/SUP], Christine Carapito[SUP] 3 4 [/SUP], Gowrishankar Ganesh[SUP] 2 7 [/SUP], Raphael Gaudin[SUP] 16 17 [/SUP]
Affiliations
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.
. 2024 Mar 28.
doi: 10.1038/s41564-024-01657-2. Online ahead of print. Brain exposure to SARS-CoV-2 virions perturbs synaptic homeostasis
Emma Partiot[SUP] 1 2 [/SUP], Aurélie Hirschler[SUP] 3 4 [/SUP], Sophie Colomb[SUP] 5 6 [/SUP], Willy Lutz[SUP] 1 2 7 [/SUP], Tine Claeys[SUP] 8 9 [/SUP], François Delalande[SUP] 3 4 [/SUP], Maika S Deffieu[SUP] 1 2 [/SUP], Yonis Bare[SUP] 1 2 [/SUP], Judith R E Roels[SUP] 10 [/SUP], Barbara Gorda[SUP] 1 2 [/SUP], Joanna Bons[SUP] 3 4 [/SUP], Domitille Callon[SUP] 11 12 [/SUP], Laurent Andreoletti[SUP] 11 12 [/SUP], Marc Labrousse[SUP] 12 13 [/SUP], Frank M J Jacobs[SUP] 10 [/SUP], Valérie Rigau[SUP] 2 14 [/SUP], Benoit Charlot[SUP] 2 15 [/SUP], Lennart Martens[SUP] 8 9 [/SUP], Christine Carapito[SUP] 3 4 [/SUP], Gowrishankar Ganesh[SUP] 2 7 [/SUP], Raphael Gaudin[SUP] 16 17 [/SUP]
Affiliations
- PMID: 38548923
- DOI: 10.1038/s41564-024-01657-2
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.