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@ARTICLE{Upadhya:277509,
author = {Upadhya, Manoj and Stumpf, Alexander and O'Brien-Cairney,
Jack and Cordero Gomez, Cesar and Döring, Jan Michael and
Hoffmann, Julius and Mueller, Susanne and Fukata, Yuko and
van Hoof, Scott and Dhangar, Divya and Wilson, Max A and
Atwal, Arunvir and Rosch, Richard and Woodhall, Gavin and
Boehm-Sturm, Philipp and Fukata, Masaki and Kreye, Jakob and
Schmitz, Dietmar and Wright, Sukhvir K and Kornau,
Hans-Christian and Prüss, Harald},
title = {{P}atient-derived monoclonal {LGI}1 autoantibodies elicit
seizures, behavioral changes and brain {MRI} abnormalities
in rodent models.},
journal = {Brain, behavior and immunity},
volume = {126},
issn = {0889-1591},
address = {Orlando, Fla. [u.a.]},
publisher = {Elsevier},
reportid = {DZNE-2025-00420},
pages = {342 - 355},
year = {2025},
abstract = {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.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.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.Our data strongly
corroborate and extend our understanding of the direct
pathogenic and epileptogenic role of human LGI1
autoantibodies.},
keywords = {Animal model (Other) / Human monoclonal antibody (Other) /
LGI1 (Other) / Limbic encephalitis (Other) / Seizure
(Other)},
cin = {AG Prüß / AG Schmitz},
ddc = {150},
cid = {I:(DE-2719)1810003 / I:(DE-2719)1810004},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 351 -
Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39984135},
doi = {10.1016/j.bbi.2025.02.019},
url = {https://pub.dzne.de/record/277509},
}