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000277509 1001_ $$aUpadhya, Manoj$$b0
000277509 245__ $$aPatient-derived monoclonal LGI1 autoantibodies elicit seizures, behavioral changes and brain MRI abnormalities in rodent models.
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000277509 520__ $$aLimbic 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.
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000277509 650_7 $$2Other$$aAnimal model
000277509 650_7 $$2Other$$aHuman monoclonal antibody
000277509 650_7 $$2Other$$aLGI1
000277509 650_7 $$2Other$$aLimbic encephalitis
000277509 650_7 $$2Other$$aSeizure
000277509 7001_ $$aStumpf, Alexander$$b1
000277509 7001_ $$aO'Brien-Cairney, Jack$$b2
000277509 7001_ $$0P:(DE-2719)9001947$$aCordero Gomez, Cesar$$b3$$udzne
000277509 7001_ $$0P:(DE-2719)2814277$$aDöring, Jan Michael$$b4
000277509 7001_ $$0P:(DE-2719)9001563$$aHoffmann, Julius$$b5$$udzne
000277509 7001_ $$aMueller, Susanne$$b6
000277509 7001_ $$aFukata, Yuko$$b7
000277509 7001_ $$0P:(DE-2719)2812820$$avan Hoof, Scott$$b8$$udzne
000277509 7001_ $$aDhangar, Divya$$b9
000277509 7001_ $$aWilson, Max A$$b10
000277509 7001_ $$aAtwal, Arunvir$$b11
000277509 7001_ $$aRosch, Richard$$b12
000277509 7001_ $$aWoodhall, Gavin$$b13
000277509 7001_ $$aBoehm-Sturm, Philipp$$b14
000277509 7001_ $$aFukata, Masaki$$b15
000277509 7001_ $$0P:(DE-2719)2811468$$aKreye, Jakob$$b16$$udzne
000277509 7001_ $$0P:(DE-2719)2810725$$aSchmitz, Dietmar$$b17$$udzne
000277509 7001_ $$aWright, Sukhvir K$$b18
000277509 7001_ $$0P:(DE-2719)2811900$$aKornau, Hans-Christian$$b19$$udzne
000277509 7001_ $$0P:(DE-2719)2810931$$aPrüss, Harald$$b20$$eLast author$$udzne
000277509 773__ $$0PERI:(DE-600)1462491-6$$a10.1016/j.bbi.2025.02.019$$gVol. 126, p. 342 - 355$$p342 - 355$$tBrain, behavior and immunity$$v126$$x0889-1591$$y2025
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