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GABA binding to neuronal GABA<jats:sub>A<\/jats:sub>R leads to a rapid hyperpolarization and a higher excitation threshold due to an increase in membrane Cl<jats:sup>\u2212<\/jats:sup> permeability. The synaptic GABA<jats:sub>A<\/jats:sub>R is mostly composed of two \u03b1(1\u20133), two \u03b2, and one \u03b3 subunit with the most abundant configuration \u03b11\u03b22\u03b32. Recently, antibodies (Abs) against \u03b11, \u03b23, and \u03b32 subunits of GABA<jats:sub>A<\/jats:sub>R were detected in a severe form of autoimmune encephalitis with refractory seizures, status epilepticus, and multifocal brain lesions, affecting gray and white matter. Experimental studies confirmed multiple mechanisms and direct functional effects of GABA<jats:sub>A<\/jats:sub>R Abs on neurons with decreased GABAergic synaptic transmission and increased neuronal excitability. The expression of GABA<jats:sub>A<\/jats:sub>R on astrocytes is well established. However, extensive studies about the effects of autoimmune GABA<jats:sub>A<\/jats:sub>R Abs on astrocytic GABA<jats:sub>A<\/jats:sub>R are missing. We hypothesize that GABA<jats:sub>A<\/jats:sub>R Abs may lead additionally to blocking astrocytic GABA<jats:sub>A<\/jats:sub>Rs with impaired Ca<jats:sup>2+<\/jats:sup> homeostasis\/spreading, astrocytic Cl<jats:sup>\u2212<\/jats:sup> imbalance, dysfunction of astrocyte\u2010mediated gliotransmission (e.g., decreased adenosine levels) and accumulation of excitatory neurotransmission, all this contributing to seizures, variable clinical\/MRI presentations, and severity. The most abundant expressed GABA<jats:sub>A<\/jats:sub>R subunits in rodent astrocytes are \u03b11, \u03b12, \u03b21, \u03b23, and \u03b31 localized in both white and gray matter. Data about GABA<jats:sub>A<\/jats:sub>R subunits in human astrocytes are even more limited, comprising \u03b12, \u03b21, and \u03b31. Overlapping binding of GABA<jats:sub>A<\/jats:sub>R Abs to neuronal and astroglial receptors is still possible. In vitro and in vivo animal models can be helpful to test the effects of GABA<jats:sub>A<\/jats:sub>R Abs on glia. This is from an epileptological point of view relevant because of the increasing evidence, confirming the glial involvement in the pathogenesis of epilepsy. Taken together, autoimmune disorders are complex and multiple mechanisms including glia could contribute to the pathogenesis of GABA<jats:sub>A<\/jats:sub>R encephalitis with seizures.<\/jats:p>","DOI":"10.1002\/epi4.12750","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T13:49:38Z","timestamp":1681998578000},"page":"692-701","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The potential role of astroglial <scp>GABA<sub>A<\/sub><\/scp> receptors in autoimmune encephalitis associated with <scp>GABA<sub>A<\/sub><\/scp> receptor antibodies and seizures"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-8056","authenticated-orcid":false,"given":"Fatme Seval","family":"Ismail","sequence":"first","affiliation":[{"name":"Department of Neurology, Klinikum Vest Academic Teaching Hospital of the Ruhr University Bochum  Recklinghausen 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