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

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

  • Nat Microbiol. 2024 May;9(5):1189-1206. doi: 10.1038/s41564-024-01657-2.
Emma Partiot 1 2,  Aurélie Hirschler 3 4,  Sophie Colomb 5 6,  Willy Lutz 1 2 7,  Tine Claeys 8 9,  François Delalande 3 4,  Maika S Deffieu 1 2,  Yonis Bare 1 2,  Judith R E Roels 10,  Barbara Gorda 1 2,  Joanna Bons 3 4,  Domitille Callon 11 12,  Laurent Andreoletti 11 12,  Marc Labrousse 12 13,  Frank M J Jacobs 10,  Valérie Rigau 2 14,  Benoit Charlot 2 15,  Lennart Martens 8 9,  Christine Carapito 3 4,  Gowrishankar Ganesh 2 7,  Raphael Gaudin 16 17
Affiliations

Affiliations

  • 1 CNRS, Institut de Recherche en Infectiologie de Montpellier (IRIM), Montpellier, France.
  • 2 Univ Montpellier, Montpellier, France.
  • 3 Laboratoire de Spectrométrie de Masse Bio-Organique, IPHC, UMR 7178, CNRS-Université de Strasbourg, Strasbourg, France.
  • 4 Infrastructure Nationale de Protéomique ProFI─FR2048, Strasbourg, France.
  • 5 EDPFM (Equipe de Droit Pénal et de Sciences Forensiques de Montpellier), Univ Montpellier, Montpellier, France.
  • 6 Emergency Pole, Forensic Medicine Department, Montpellier University Hospital, Montpellier, France.
  • 7 UM-CNRS Laboratoire d'Informatique de Robotique et de Microelectronique de Montpellier (LIRMM), Montpellier, France.
  • 8 VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium.
  • 9 Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.
  • 10 Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
  • 11 University of Reims Champagne-Ardenne, Medicine Faculty, Laboratory of Virology, CardioVir UMR-S 1320, Reims, France.
  • 12 Forensic, Virology and ENT Departments, University Hospital Centre (CHU), Reims, France.
  • 13 Anatomy laboratory, UFR Médecine, Université de Reims Champagne-Ardenne, Reims, France.
  • 14 Pathological Department and Biological Resources Center BRC, Montpellier University Hospital, 'Cerebral plasticity, Stem cells and Glial tumors' team. IGF- Institut de génomique fonctionnelle INSERM U 1191 - CNRS UMR 5203, Univ Montpellier, Montpellier, France.
  • 15 Institut d'Electronique et des Systèmes (IES), CNRS, Montpellier, France.
  • 16 CNRS, Institut de Recherche en Infectiologie de Montpellier (IRIM), Montpellier, France. [email protected].
  • 17 Univ Montpellier, Montpellier, France. [email protected].
PMID: 38548923 DOI: 10.1038/s41564-024-01657-2
Abstract

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.

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