Differences in ionotropic glutamate receptor subunit expression are not responsible for strain-dependent susceptibility to excitotoxin-induced injury.
Systemic administration of kainic acid in C57BL/6 and FVB/N mice induces a comparable level of seizure induction yet results in differential susceptibility to seizure-induced cell death. While kainate administration causes severe hippocampal damage in mice of the FVB/N strain, C57BL/6 mice display no demonstrable cell loss or damage. At present, while the cellular mechanisms underlying strain-dependent differences in susceptibility remain unclear, some of this variation is assumed to have a genetic basis. As glutamate receptors are thought to participate in seizure induction and the subsequent neuronal degeneration that ensues, previous studies have proposed that variation in the precise subunit composition of glutamate receptors may result in differential susceptibility to excitotoxic cell death. Thus, we chose to examine the relationship between the cellular distribution and expression of glutamate receptor subunit proteins and cell loss within the hippocampus in mouse strains resistant and susceptible to kainate-induced excitotoxicity. Using semi-quantitative Western blot techniques and immunohistochemistry with the use of antibodies that recognize subunits of the KA (GluR5,6,7), AMPA (GluR1, GluR2, and GluR4), and NMDA (NMDAR1 and NMDAR2A/2B) receptors, we found no significant strain-dependent differences in the expression or distribution of these glutamate receptor subunits in the intact hippocampus. Following kainate administration, expression changes in ionotropic glutamate receptor subunits paralleled the development of susceptibility to cell death in the FVB/N strain only. Strain differences in hippocampal vulnerability to kainate-induced status epilepticus are not due to glutamate receptor protein expression.
Schauwecker
Paula Elyse
PE
Department of Cell and Neurobiology, University of Southern California, Keck School of Medicine, BMT 401, 1333 San Pablo Street, Los Angeles, CA 90089-9112, USA. schauwec@usc.edu
D000818:Animals; D016923:Cell Death / Q000235:genetics*; D004195:Disease Models, Animal; D004351:Drug Resistance / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018698:Glutamic Acid / Q000378:metabolism / Q000633:toxicity; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000378:metabolism / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009498:Neurotoxins / Q000378:metabolism / Q000633:toxicity; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
D018698:Glutamic Acid; D007608:Kainic Acid; D009498:Neurotoxins; D021122:Protein Subunits; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate