Human NMDAR autoantibodies disrupt excitatory-inhibitory balance, leading to hippocampal network hypersynchrony.
| Autor: | Ceanga M; Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, 07747 Jena, Germany., Rahmati V; Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, 07747 Jena, Germany., Haselmann H; Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, 07747 Jena, Germany., Schmidl L; Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, 07747 Jena, Germany., Hunter D; Université de Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France., Brauer AK; Institute of Clinical Neuroimmunology, Klinikum der Universität München, Ludwig Maximilians University Munich, Martinsried, Germany; Biomedical Center, Ludwig Maximilians University Munich, Martinsried, Germany., Liebscher S; Institute of Clinical Neuroimmunology, Klinikum der Universität München, Ludwig Maximilians University Munich, Martinsried, Germany; Biomedical Center, Ludwig Maximilians University Munich, Martinsried, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Kreye J; Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany; Department of Pediatric Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany., Prüss H; Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany., Groc L; Université de Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France., Hallermann S; Carl Ludwig Institute for Physiology, Faculty of Medicine, Leipzig University, 04103 Leipzig, Germany., Dalmau J; Catalan Institution for Research and Advanced Studies (ICREA) and IDIBAPS-Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain., Ori A; Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), 07745 Jena, Germany., Heckmann M; Department of Neurophysiology, Institute of Physiology, University of Würzburg, 97070 Würzburg, Germany., Geis C; Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, 07747 Jena, Germany. Electronic address: christian.geis@med.uni-jena.de. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Cell reports [Cell Rep] 2023 Oct 31; Vol. 42 (10), pp. 113166. Date of Electronic Publication: 2023 Sep 27. |
| DOI: | 10.1016/j.celrep.2023.113166 |
| Abstrakt: | Anti-NMDA receptor autoantibodies (NMDAR-Abs) in patients with NMDAR encephalitis cause severe disease symptoms resembling psychosis and cause cognitive dysfunction. After passive transfer of patients' cerebrospinal fluid or human monoclonal anti-GluN1-autoantibodies in mice, we find a disrupted excitatory-inhibitory balance resulting from CA1 neuronal hypoexcitability, reduced AMPA receptor (AMPAR) signaling, and faster synaptic inhibition in acute hippocampal slices. Functional alterations are also reflected in widespread remodeling of the hippocampal proteome, including changes in glutamatergic and GABAergic neurotransmission. NMDAR-Abs amplify network γ oscillations and disrupt θ-γ coupling. A data-informed network model reveals that lower AMPAR strength and faster GABA Competing Interests: Declaration of interests J.D. receives royalties from Euroimmun for the use of the NMDA receptor as an antibody test. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|