{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hunter D"],"funding":["Académie Nationale de Médecine","Interdisziplinäres Zentrum für Klinische Forschung","Foundation Else Kröner-Fresenius-Stiftung","Deutsche Forschungsgemeinschaft (DFG)","Agence Nationale de la Recherche (ANR)","Agence Nationale de la Recherche","Helmholtz Association","GPR BRAIN Université de Bordeaux","German Federal Ministry of Education and Research","Helmholtz Association ()","EC | Horizon Europe | Excellent Science | HORIZON EUROPE Marie Sklodowska-Curie Actions","European Research Council","Deutsche Forschungsgemeinschaft","EC | Horizon Europe | Excellent Science | HORIZON EUROPE Marie Sklodowska-Curie Actions (MSCA)","Fondation pour la Recherche Médicale (FRM)","Centre National de la Recherche Scientifique","Fondation pour la Recherche Médicale","Era-Net Neuron"],"pagination":["1623-1649"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10933378"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(3)"],"pubmed_abstract":["Psychiatric and neurological symptoms, as well as cognitive deficits, represent a prominent phenotype associated with variable forms of autoimmune encephalitis, regardless of the neurotransmitter receptor targeted by autoantibodies. The mechanistic underpinnings of these shared major neuropsychiatric symptoms remain however unclear. Here, we investigate the impacts of patient-derived monoclonal autoantibodies against the glutamatergic NMDAR (NMDAR mAb) and inhibitory GABAaR (GABAaR mAb) signalling in the hippocampal network. Unexpectedly, both excitatory and inhibitory synaptic receptor membrane dynamics, content and transmissions are altered by NMDAR or GABAaR mAb, irrespective of the affinity or antagonistic effect of the autoantibodies. The effect of NMDAR mAb on inhibitory synapses and GABAaR mAb on excitatory synapses requires neuronal activity and involves protein kinase signalling. At the cell level, both autoantibodies increase the excitation/inhibition balance of principal cell inputs. Furthermore, NMDAR or GABAaR mAb leads to hyperactivation of hippocampal networks through distinct alterations of principal cell and interneuron properties. Thus, autoantibodies targeting excitatory NMDAR or inhibitory GABAaR trigger convergent network dysfunctions through a combination of shared and distinct mechanisms."],"journal":["EMBO reports"],"pubmed_title":["Converging synaptic and network dysfunctions in distinct autoimmune encephalitis."],"pmcid":["PMC10933378"],"funding_grant_id":["Autoscale 01EW1901","FOR3004,PR1274/3-1,PR1274/5-1,and PR1274/9-1","813986","HIL-A03","01GM1908D","GE2519/8-1,GE2519/9-1,GE 2519/11-1","201909009269","DopamineHub","IZKF","951294","951294 Synergy"],"pubmed_authors":["Hunter D","Fernandes D","Rodrigues C","Geis C","Kreye J","Groc L","Pruss H","Benac N","Petit-Pedrol M","Ceanga M"],"additional_accession":[]},"is_claimable":false,"name":"Converging synaptic and network dysfunctions in distinct autoimmune encephalitis.","description":"Psychiatric and neurological symptoms, as well as cognitive deficits, represent a prominent phenotype associated with variable forms of autoimmune encephalitis, regardless of the neurotransmitter receptor targeted by autoantibodies. The mechanistic underpinnings of these shared major neuropsychiatric symptoms remain however unclear. Here, we investigate the impacts of patient-derived monoclonal autoantibodies against the glutamatergic NMDAR (NMDAR mAb) and inhibitory GABAaR (GABAaR mAb) signalling in the hippocampal network. Unexpectedly, both excitatory and inhibitory synaptic receptor membrane dynamics, content and transmissions are altered by NMDAR or GABAaR mAb, irrespective of the affinity or antagonistic effect of the autoantibodies. The effect of NMDAR mAb on inhibitory synapses and GABAaR mAb on excitatory synapses requires neuronal activity and involves protein kinase signalling. At the cell level, both autoantibodies increase the excitation/inhibition balance of principal cell inputs. Furthermore, NMDAR or GABAaR mAb leads to hyperactivation of hippocampal networks through distinct alterations of principal cell and interneuron properties. Thus, autoantibodies targeting excitatory NMDAR or inhibitory GABAaR trigger convergent network dysfunctions through a combination of shared and distinct mechanisms.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-06-30T03:10:04.375Z","creation":"2025-04-06T14:31:22.983Z"},"accession":"S-EPMC10933378","cross_references":{"pubmed":["38253690"],"doi":["10.1038/s44319-024-00056-2"]}}