{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:05:57Z","timestamp":1790661957735,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Research Council through grant &quot;Munich Cluster for Systems Neurology (SyNergy, grant EXC 2145, projekt ID 390857198)&quot;","award":["grant EXC 2145, projekt ID 390857198"],"award-info":[{"award-number":["grant EXC 2145, projekt ID 390857198"]}]},{"name":"German Federal Ministry of Science and Education (Comprehensive, Orchestrated, National Network to Explain, Categorize and Treat autoimmune encephalitis and allied diseases within the German NEtwork for Research on AuToimmune Encephalitis \u2013 CONNECT GENERA","award":["01GM1908"],"award-info":[{"award-number":["01GM1908"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autoimmune encephalitis associated with antibodies (Abs) against \u03b11, \u03b23, and \u03b32 subunits of \u03b3-aminobutyric acid receptor A (GABAAR) represents a severe form of encephalitis with refractory seizures and status epilepticus. Reduction in inhibitory GABAergic synaptic activity is linked to dysfunction of neuronal networks, hyperexcitability, and seizures. The aim in this study was to investigate the direct pathogenic effect of a recombinant GABAAR autoantibody (rAb-IP2), derived from the cerebrospinal fluid (CSF) of a patient with autoimmune GABAAR encephalitis, on hippocampal CA1 and CA3 networks. Acute brain slices from C57BL\/6 mice were incubated with rAb-IP2. The spontaneous synaptic GABAergic transmission was measured using electrophysiological recordings in voltage-clamp mode. The GABAAR autoantibody rAb-IP2 reduced inhibitory postsynaptic signaling in the hippocampal CA1 pyramidal neurons with regard to the number of spontaneous inhibitory postsynaptic currents (sIPSCs) but did not affect their amplitude. In the hippocampal CA3 network, decreased number and amplitude of sIPSCs were detected, leading to decreased GABAergic synaptic transmission. Immunohistochemical staining confirmed the rAb-IP2 bound to hippocampal tissue. These findings suggest that GABAAR autoantibodies exert direct functional effects on both hippocampal CA1 and CA3 pyramidal neurons and play a crucial role in seizure generation in GABAAR autoimmune encephalitis.<\/jats:p>","DOI":"10.3390\/ijms23073707","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:44:52Z","timestamp":1648590292000},"page":"3707","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["GABAA Receptor Autoantibodies Decrease GABAergic Synaptic Transmission in the Hippocampal CA3 Network"],"prefix":"10.3390","volume":"23","author":[{"given":"Am\u00e9lie F.","family":"Menke","sequence":"first","affiliation":[{"name":"Department of Neurology, Institute of Translational Neurology, University of M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatme Seval","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Knappschaftskrankenhaus Bochum, Ruhr University Bochum, 44892 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Dornmair","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neuroimmunology, Biomedical Center and Hospital of the Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 82152 Martinsried, Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 81377 M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Cerina","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Translational Neurology, University of M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven G.","family":"Meuth","sequence":"additional","affiliation":[{"name":"Department of Neurology, Heinrich-Heine University of D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2420-701X","authenticated-orcid":false,"given":"Nico","family":"Melzer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Heinrich-Heine University of D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nrn2370","article-title":"GABA(A) receptor trafficking and its role in the dynamic modulation of neuronal inhibition","volume":"9","author":"Jacob","year":"2008","journal-title":"Nat. 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