title: Increased spontaneous activity of a network of hippocampal neurons in culture caused by suppression of inhibitory potentials mediated by anti-gad antibodies.
abstract: BACKGROUND
  Anti-glutamic acid decarboxylase autoantibodies (GAD-Ab) are commonly considered the marker of autoimmune diabetes; they were first described in patients affected by stiff-person syndrome and recently, in ataxic or epileptic patients. The pathogenetic role of GAD-Ab remains unclear but inhibition of GABA synthesis or interference with GABA exocytosis are hypothesized. The aim of the study was to assess whether GAD-Ab interfere with neuronal transmission.
  
  
  METHODS
  Serum from a GAD-Ab positive epileptic patient (by IHC and RIA), serum from a GAD-positive (only by RIA) diabetic case, sera from two epileptic GAD-Ab negative patients and a normal control were selected. Post-synaptic inhibitory potentials (IPSPs) were registered on hippocampal neurons in culture before and after the application of diluted sera in a patch clamp study.
  
  
  RESULTS
  A significant increase in the frequency of IPSPs was observed after application of GAD-positive epileptic serum, while no effect was noted using sera from negative controls.
  
  
  CONCLUSIONS
  The inhibition in neuronal transmission only after application of GAD-positive epileptic serum, suggests an interference with GABA function and consequently with neuronal inhibition supporting a pathogenetic role of GAD-Ab in the development of epilepsy.
authors.affiliation: Department of Neurology, Ca' Foncello General Hospital, Treviso, Italy. marikavianello@libero.it
authors.forename: Marika
authors.initials: M
authors.lastname: Vianello
authors.forename: Giacomo
authors.initials: G
authors.lastname: Bisson
authors.forename: Marco
authors.initials: M
authors.lastname: Dal Maschio
authors.forename: Stefano
authors.initials: S
authors.lastname: Vassanelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Girardi
authors.forename: Carla
authors.initials: C
authors.lastname: Mucignat
authors.forename: Kostantinos
authors.initials: K
authors.lastname: Fountzoulas
authors.forename: Bruno
authors.initials: B
authors.lastname: Giometto
mesh_terms: D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000276:immunology / Q000503:physiopathology; D004827:Epilepsy / Q000276:immunology / Q000503:physiopathology; D005968:Glutamate Decarboxylase / Q000097:blood / Q000276:immunology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D006801:Humans; D053444:Inhibitory Postsynaptic Potentials; D008297:Male; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001323:Autoantibodies; D005968:Glutamate Decarboxylase