title: Serum from a Patient with GAD65 Antibody-Associated Limbic Encephalitis Did Not Alter GABAergic Neurotransmission in Cultured Hippocampal Networks.
abstract: BACKGROUND
  Glutamate decarboxylase is an intracellular enzyme converting glutamate into GABA. Antibodies (abs) to its isoform GAD65 were described in limbic encephalitis and other neurological conditions. The significance of GAD65 abs for epilepsy is unclear, but alterations of inhibitory GABAergic neurotransmission may be involved. Here, we investigated the effects of the serum of a female patient suffering from GAD65 ab-associated LE on GABAA currents in cultured hippocampal networks.
  
  
  METHODS
  Spontaneous or evoked post-synaptic GABAA currents were measured in cultured hippocampal neurons prepared from embryonic mice after 11-21 days in vitro using the patch-clamp technique in the whole-cell mode after incubation with serum of a healthy control or the LE-patient at a final concentration of 1% for 5-8 h.
  
  
  RESULTS
  Properties of miniature inhibitory post-synaptic currents were not different in cultures treated with control and LE-serum. Likewise, paired-pulse ratio of evoked GABAA currents as a measure of release probability was not different in both conditions. Evoked GABAA currents were significantly depressed during 10 Hz stimulation without significant differences between control and LE-serum treated cultures.
  
  
  CONCLUSIONS
  In our experimental paradigms, serum of a patient with confirmed GAD65 ab-associated LE had no apparent effect on GABAergic neurotransmission in murine-cultured hippocampal networks. These results challenge the view that the presence of GAD65 abs invariably compromise inhibitory network function.
authors.affiliation: Department of Epileptology, University Hospital Bonn , Bonn , Germany.
authors.forename: Nelly
authors.initials: N
authors.lastname: Stemmler
authors.affiliation: Department of Epileptology, University Hospital Bonn , Bonn , Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Rohleder
authors.affiliation: Department of Epileptology, University Hospital Bonn , Bonn , Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Malter
authors.affiliation: Department of Epileptology, University Hospital Bonn , Bonn , Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Widman
authors.affiliation: Department of Epileptology, University Hospital Bonn , Bonn , Germany.
authors.forename: Christian E
authors.initials: CE
authors.lastname: Elger
authors.affiliation: Department of Epileptology, University Hospital Bonn , Bonn , Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Beck
authors.affiliation: Department of Epileptology, University Hospital Bonn , Bonn , Germany ; Center for Rare Diseases Bonn (ZSEB), University Hospital Bonn , Bonn , Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Surges
keywords: GABA(A) currents; GABAergic neurotransmission; GAD65 antibodies; hippocampal cultures; limbic encephalitis