title: Glutamate receptor antibodies directed against AMPA receptors subunit 3 peptide B (GluR3B) can be produced in DBA/2J mice, lower seizure threshold and induce abnormal behavior.
abstract: OBJECTIVE
  Anti-GluR3B antibodies (GluR3B Ab's), directed against peptide B/aa372-395 of GluR3 subunit of glutamate/AMPA receptors, are found in ∼35% of epilepsy patients, activate glutamate/AMPA receptors, evoke ion currents, kill neurons and damage the brain. We recently found that GluR3B Ab's also associate with neurological/psychiatric/behavioral abnormalities in epilepsy patients. Here we asked if GluR3B Ab's could be produced in DBA/2J mice, and also modulate seizure threshold and/or cause behavioral/motor impairments in these mice.
  
  
  METHODS
  DBA/2J mice were immunized with the GluR3B peptide in Complete Freund's Adjuvant (CFA), or with controls: ovalbumin (OVA), CFA, or phosphate-buffer saline (PBS). GluR3B Ab's and OVA Ab's were tested. Seizures were induced in all mice by the chemoconvulsant pentylenetetrazole (PTZ) at three time points, each time with less PTZ to avoid non-specific death. Behavior was examined in Open-Field, RotaRod and Grip tests.
  
  
  RESULTS
  GluR3B Ab's were produced only in GluR3B-immunized mice, while OVA Ab's were produced only in OVA-immunized mice, showing high Ab's specificity. In GluR3B Ab's negative mice, seizure severity scores and percentages of animals developing generalized seizures declined in response to decreasing PTZ doses. In contrast, both parameters remained unchanged/high in the GluR3B Ab's positive mice, showing that these mice were more susceptible to seizures. The seizure scores associated significantly with the GluR3B Ab's levels. GluR3B Ab's positive mice were also more anxious in Open-Field test, fell faster in RotaRod test, and fell more in Grip test, compared to all the control mice.
  
  
  CONCLUSIONS
  GluR3B Ab's are produced in DBA/2J mice, facilitate seizures and induce behavioral/motor impairments. This animal model can therefore serve for studying autoimmune epilepsy and abnormal behavior mediated by pathogenic anti-GluR3B Ab's.
authors.affiliation: Department of Infection, Immunity and Inflammation, Cochin Institute, INSERM U1016, CNRS UMR8104, Paris Descartes University, Paris, France.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Ganor
authors.affiliation: Epilepsy Center, Schneider Children's Medical Center of Israel, Petah Tiqwa, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Hadassa
authors.initials: H
authors.lastname: Goldberg-Stern
authors.affiliation: Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ran
authors.initials: R
authors.lastname: Cohen
authors.affiliation: Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Vivian
authors.initials: V
authors.lastname: Teichberg
authors.affiliation: School of Behavioral Sciences, Academic College of TLV Yaffo, Israel. Electronic address: mialevite@mta.ac.il.
authors.forename: Mia
authors.initials: M
authors.lastname: Levite
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001522:Behavior, Animal / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D018091:Receptors, AMPA / Q000276:immunology*; D012640:Seizures / Q000276:immunology* / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3
keywords: Autoimmune epilepsy; Behavior; Epilepsy; GluR3 antibodies; GluR3B antibodies; Glutamate receptor antibodies; PTZ; Seizures