Immunization with the glutamate receptor-derived peptide GluR3B induces neuronal death and reactive gliosis, but confers partial protection from pentylenetetrazole-induced seizures.
Do autoantibodies (Ab's) against glutamate/AMPA receptor subtype 3 affect the severity of seizures? Rats immunized with the GluR3B-peptide (amino acids (aa) 372-395) or with the control GluR3A-peptide (aa 245-274) produced the respective anti-GluR3B and anti-GluR3A Ab's (both types of Ab's found in some epilepsy patients). The GluR3B-immunized rats exhibited neuronal death and reactive gliosis in the brain, but not overt spontaneous seizures. Surprisingly, in response to the chemoconvulsant pentylenetetrazole, the GluR3B-immunized rats displayed fewer jerks, a lower percentage of generalized seizures, and a lower overall seizure-severity score than GluR3A-immunized, scrambled GluR3B-immunized or non-immunized control rats. These findings, combined with the previously demonstrated ability of anti-GluR3B Ab's to bind, activate, and kill neurons and glia, suggest that if these Ab's are present in the brain they may cause neuronal death, which by itself may be pro-epileptic, but they may also decrease the excitability of seizure-related neural circuits, thereby conferring partial protection from seizures induced by other exogenously applied epileptogenic stimuli. The present results could have clinical implications for epilepsy.
Ganor
Yonatan
Y
Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Gottlieb
Miroslav
M
Eilam
Raya
R
Otmy
Hanoch
H
Teichberg
Vivian I
VI
Levite
Mia
M
D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000134:cerebrospinal fluid / Q000633:toxicity*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000502:physiology; D000089622:Doublecortin Domain Proteins; D005260:Female; D015686:Gene Products, env; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced*; D007114:Immunization / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D010433:Pentylenetetrazole; D010446:Peptide Fragments / Q000276:immunology / Q000633:toxicity; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D018091:Receptors, AMPA / Q000008:administration & dosage* / Q000276:immunology; D012640:Seizures / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control*
D001323:Autoantibodies; D000089622:Doublecortin Domain Proteins; D015686:Gene Products, env; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010446:Peptide Fragments; D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3; C093834:peptide fragment P828; D010751:Phosphopyruvate Hydratase; D010433:Pentylenetetrazole