Julie Jézéquel, Laurent Groc et al. dans Nature commun.

Dynamic disorganization of synaptic NMDA receptors triggered by autoantibodies from psychotic patients. Julie Jézéquel, Emily M. Johansson, Julien P. Dupuis, Véronique Rogemond, Hélène Gréa, Blanka Kellermayer, Nora Hamdani, Emmanuel Le Guen, Corentin Rabu, Marilyn Lepleux, Marianna Spatola, Elodie Mathias, Delphine Bouchet, Amy J. Ramsey, Robert H. Yolken, Ryad Tamouza, Josep Dalmau, Jérôme Honnorat, Marion Leboyer & Laurent Groc. Nature Communications 8, Article number: 1791 (2017) doi:10.1038/s41467-017-01700-3 Published online: 27 November 2017

Laurent GROC Directeur Recherche CNRS, Group Leader IINS,
Julie JEZEQUEL, Postdoctoral Research Assistant, King’s College London, Department of  Developmental Neurobiology & Université de Bordeaux , Bordeaux Neurocampus

The flourishing identification of circulating autoantibodies against neuronal receptors in neuropsychiatric disorders has fostered new conceptual and clinical frameworks. However, their putative presence in different diseases, as well as in healthy subjects, has raised questions about detection reliability and pathogenic role.

Laurent Groc, Julie Jézéquel:In a translational study with clinical experts from Europe and US, Julie Jezequel and collaborators have use single molecule-based imaging approaches to ascertain the presence of circulating autoantibodies against glutamate NMDA receptor (NMDAR-Ab) in about 20% of psychotic patients diagnosed with schizophrenia and very few healthy subjects. Strikingly, NMDAR-Ab from patients, but not from healthy subjects, specifically alter the surface dynamics and nanoscale organization of synaptic NMDAR and its anchoring partner the EphrinB2 receptor. Functionally, only patients’ NMDAR-Ab prevent long-term potentiation at glutamatergic synapses while leaving NMDAR-mediated calcium influx intact.

Thus, by taking advantage of the single molecule imaging, we unveil that NMDAR-Ab from psychotic patients profoundly alter NMDAR synaptic transmission, supporting a pathogenically relevant role. This work sheds thus new and unsuspected ligth on the dysfunction of NMDAR signaling in psychotic disorders.