Human Autoantibodies against the AMPA Receptor Subunit GluA2 Induce Receptor Reorganization and Memory Dysfunction

Neuron
Holger HaselmannChristian Geis

Abstract

AMPA receptors are essential for fast excitatory transmission in the CNS. Autoantibodies to AMPA receptors have been identified in humans with autoimmune encephalitis and severe defects of hippocampal function. Here, combining electrophysiology and high-resolution imaging with neuronal culture preparations and passive-transfer models in wild-type and GluA1-knockout mice, we analyze how specific human autoantibodies against the AMPA receptor subunit GluA2 affect receptor function and composition, synaptic transmission, and plasticity. Anti-GluA2 antibodies induce receptor internalization and a reduction of synaptic GluA2-containing AMPARs followed by compensatory ryanodine receptor-dependent incorporation of synaptic non-GluA2 AMPARs. Furthermore, application of human pathogenic anti-GluA2 antibodies to mice impairs long-term synaptic plasticity in vitro and affects learning and memory in vivo. Our results identify a specific immune-neuronal rearrangement of AMPA receptor subunits, providing a framework to explain disease symptoms.

Citations

Sep 14, 2018·Nature Reviews. Neuroscience·Darran Yates
Feb 5, 2019·The Journal of Clinical Investigation·Christian GeisJosep Dalmau
Oct 9, 2019·Brain : a Journal of Neurology·Sarah J CrispDimitri M Kullmann
May 28, 2020·Nature Reviews. Neurology·Francesc GrausJosep Dalmau
Apr 17, 2019·Nature Reviews. Neurology·Katrin PapeFrauke Zipp
Oct 17, 2019·Annals of Clinical and Translational Neurology·Michele RomoliPaolo Calabresi
Jul 17, 2020·International Journal of Molecular Sciences·Hiroshi MitomaMario Manto
Aug 14, 2019·Frontiers in Neurology·Tetyana Blinder, Jan Lewerenz
Sep 3, 2020·Translational Psychiatry·L L GibsonT A Pollak
Dec 19, 2018·Journal of Neurology·Osvaldo Laurido-SotoGregory S Day
May 14, 2019·Frontiers in Neurology·Niels Hansen
Jun 27, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Khalil S Husari, Divyanshu Dubey
Mar 13, 2020·Proceedings of the National Academy of Sciences of the United States of America·Maryann P PlattDritan Agalliu
Mar 3, 2020·Frontiers in Neurology·Maria Pia GiannoccaroAngela Vincent
Oct 28, 2019·Journal of Neurology·Sudarshini RamanathanSarosh R Irani
Jun 13, 2020·Science·Laurent Groc, Daniel Choquet
Oct 8, 2020·Journal of Neural Transmission·Niels Hansen, Charles Timäus
Nov 26, 2020·Expert Opinion on Therapeutic Targets·Josefine SellChristian Geis
Nov 21, 2020·Journal of Experimental Botany·Kati MielkeChristiane Funk
Nov 20, 2020·Lancet Neurology·Amaia Muñoz-LopetegiJoan Santamaria
Jan 16, 2021·Journal of the Neurological Sciences·Tatsuya FukumotoYuishin Izumi
Mar 24, 2021·Chemical Reviews·Christian WernerChristian Geis
May 18, 2020·Current Opinion in Neurobiology·Daniel Choquet, Eric Hosy
Apr 30, 2021·Neuropharmacology·Jeremy M HenleyKevin A Wilkinson
May 13, 2021·Nature Reviews. Immunology·Harald Prüss
May 6, 2021·Annals of Neurology·Jon LandaUNKNOWN GluK2 encephalitis study group
May 22, 2021·Neurology. Neuroimmunology and Neuroinflammation·Gerda RickenRomana Höftberger
Jun 8, 2021·Frontiers in Immunology·Tian-Yi ZhangYin-Xi Zhang
Jul 12, 2021·Brain, Behavior, and Immunity·Diego ScheggiaFabrizio Gardoni
Mar 22, 2020·Epilepsy & Behavior : E&B·Niels HansenChristian E Elger
Nov 21, 2021·The Journal of Allergy and Clinical Immunology·Josep Dalmau, Francesc Graus
Dec 14, 2021·Frontiers in Synaptic Neuroscience·Alexander KuhlemannChristian Werner

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