Increased spontaneous activity of a network of hippocampal neurons in culture caused by suppression of inhibitory potentials mediated by anti-gad antibodies.
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.
Vianello
Marika
M
Department of Neurology, Ca' Foncello General Hospital, Treviso, Italy. marikavianello@libero.it
Bisson
Giacomo
G
Dal Maschio
Marco
M
Vassanelli
Stefano
S
Girardi
Stefano
S
Mucignat
Carla
C
Fountzoulas
Kostantinos
K
Giometto
Bruno
B
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
D001323:Autoantibodies; D005968:Glutamate Decarboxylase