{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Upadhya M"],"funding":["German Research Foundation","Aston University","Helmholtz Association of German Research Centres","Federal Ministry of Education and Research Bonn Office","Japan Agency for Medical Research and Development","Wellcome Trust"],"pagination":["342-355"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7618076"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["126"],"pubmed_abstract":["<h4>Objective</h4>Limbic encephalitis with leucine-rich glioma inactivated 1 (LGI1) protein autoantibodies is associated with cognitive impairment, psychiatric symptoms, and seizures, including faciobrachial dystonic seizures (FBDS). Patient-derived LGI1-autoantibodies cause isolated symptoms of memory deficits in mice and seizures in rats. Using a multimodal experimental approach, we set out to improve the validity of existing in vivo rodent models to further recapitulate the full clinical syndrome of anti-LGI1 antibody mediated disease.<h4>Methods</h4>A monoclonal anti-LGI1 antibody (anti-LGI1 mAb) derived from a patient's CSF antibody-secreting cell was infused intracerebroventricularly (ICV) into rats and mice for one or two weeks, respectively. Cellular excitability of CA3 pyramidal neurons was determined in hippocampal slices. Structural changes in mouse brains were explored using MRI. Antibody effects on behavior and brain activity of rats were studied using video-EEG.<h4>Results</h4>Anti-LGI1 mAbs augmented the excitability of CA3 pyramidal neurons and elicited convulsive and non-convulsive spontaneous epileptic seizures in mice and rats. Mice displayed a hypoactive and anxious phenotype during behavioral testing. MRI revealed acutely increased hippocampal volume after ICV anti-LGI1 mAb infusion. Video-EEG recordings of juvenile rats uncovered two peaks of seizure frequency during the 7-day antibody infusion period resembling the natural progression of seizures in human anti-LGI1 encephalitis.<h4>Interpretation</h4>Our data strongly corroborate and extend our understanding of the direct pathogenic and epileptogenic role of human LGI1 autoantibodies."],"journal":["Brain, behavior, and immunity"],"pubmed_title":["Patient-derived monoclonal LGI1 autoantibodies elicit seizures, behavioral changes and brain MRI abnormalities in rodent models."],"pmcid":["PMC7618076"],"funding_grant_id":["01EW2305","01EW1811","EXC-2049 \\u2013 390688087","415914819","JP24wm0625319","216613/Z/19/Z","415914819 \\u2212 FOR 3004","504745852 \\u2013 KFO 5023","JP24ek0109649","FOR 3004"],"pubmed_authors":["Rosch R","Doring J","Fukata Y","O'Brien-Cairney J","Gomez CC","Upadhya M","Kornau HC","Atwal A","Fukata M","van Hoof S","Schmitz D","Wright SK","Wilson MA","Hoffmann J","Kreye J","Dhangar D","Woodhall G","Pruss H","Boehm-Sturm P","Mueller S","Stumpf A"],"additional_accession":[]},"is_claimable":false,"name":"Patient-derived monoclonal LGI1 autoantibodies elicit seizures, behavioral changes and brain MRI abnormalities in rodent models.","description":"<h4>Objective</h4>Limbic encephalitis with leucine-rich glioma inactivated 1 (LGI1) protein autoantibodies is associated with cognitive impairment, psychiatric symptoms, and seizures, including faciobrachial dystonic seizures (FBDS). Patient-derived LGI1-autoantibodies cause isolated symptoms of memory deficits in mice and seizures in rats. Using a multimodal experimental approach, we set out to improve the validity of existing in vivo rodent models to further recapitulate the full clinical syndrome of anti-LGI1 antibody mediated disease.<h4>Methods</h4>A monoclonal anti-LGI1 antibody (anti-LGI1 mAb) derived from a patient's CSF antibody-secreting cell was infused intracerebroventricularly (ICV) into rats and mice for one or two weeks, respectively. Cellular excitability of CA3 pyramidal neurons was determined in hippocampal slices. Structural changes in mouse brains were explored using MRI. Antibody effects on behavior and brain activity of rats were studied using video-EEG.<h4>Results</h4>Anti-LGI1 mAbs augmented the excitability of CA3 pyramidal neurons and elicited convulsive and non-convulsive spontaneous epileptic seizures in mice and rats. Mice displayed a hypoactive and anxious phenotype during behavioral testing. MRI revealed acutely increased hippocampal volume after ICV anti-LGI1 mAb infusion. Video-EEG recordings of juvenile rats uncovered two peaks of seizure frequency during the 7-day antibody infusion period resembling the natural progression of seizures in human anti-LGI1 encephalitis.<h4>Interpretation</h4>Our data strongly corroborate and extend our understanding of the direct pathogenic and epileptogenic role of human LGI1 autoantibodies.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 May","modification":"2026-04-08T16:07:19.933Z","creation":"2026-04-08T06:05:20.433Z"},"accession":"S-EPMC7618076","cross_references":{"pubmed":["39984135"],"doi":["10.1016/j.bbi.2025.02.019"]}}