Effect of antibodies against AMPA glutamate receptors on brain neurons in primary cultures of the cerebellum and hippocampus.
Rabbit antibodies against GluR1 subunit of AMPA glutamate receptors in a concentration of 1 mug/ml significantly increased intracellular Ca(2+)concentration and decreased mitochondrial potential in hippocampal neurons, i.e. produced changes typical of the influence of glutamate in toxic concentrations. In cerebellar neurons rabbit antibodies potentiated glutamate-induced increase in intracellular Ca(2+)concentration and significantly decreased the mitochondrial potential (compared to the level observed after application of glutamate alone). The exposure of cultured cerebellar neurons to antibodies in a concentration of 0.1 mug/ml for 24 h was followed by a 50% decrease in ATP concentration and development of neuronal necrosis. Our results attest to an important role of autoimmune damage to neurons during hyperstimulation of glutamate receptors.
Sorokina
E G
EG
Laboratory of Membranology, Scientific Center for Children's Health, Russian Academy of Medical Sciences, Moscow. sorokina@nczd.ru
Storozhevykh
T P
TP
Senilova
Ya E
YE
Granstrem
O K
OK
Reutov
V P
VP
Pinelis
V G
VG
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000276:immunology*
D000906:Antibodies; D018091:Receptors, AMPA; D000255:Adenosine Triphosphate; D002118:Calcium