Short communication Differential regulation of apoptosis-related genes in resistant and vulnerable subfields of the rat epileptic hippocampus

Animals exposed to kainic acid KA induced status epilepticus display a striking pattern of selective neuronal vulnerability in the . hippocampus. Neurons in the hilusrCA3 and CA1 subfields appear particularly sensitive whereas dentate gyrus DG granule cells are resistant. The molecular basis for this differential susceptibility remains largely unknown. Recently, an involvement of nitric oxide, c-Jun . . amino-terminal kinases JNK and interleukin-1 b converting enzyme ICE -related proteases has been proposed in KA induced neuronal cell death. In the present study, we have determined the regional expression of transcripts for two modulating genes operating in these . pathways, i.e., the endogenous protein inhibitor of neuronal nitric oxide synthase PIN , and a cytoplasmic inhibitor of the JNK signal . transduction pathway, designated JNK interacting protein-1 JIP-1 and of the gene for the apoptosis-executing protease Caspase-3 in KA-treated animals. The expression of PIN and JIP-1 was found significantly upregulated in granule cells of the resistant DG. In contrast, an induction of the ICE-related protease Caspase-3 was observed in vulnerable hippocampal regions, i.e. CA1, CA3 and hilus. These results point towards PIN and JIP-1 as antiapoptotic factors contributing to selective resistance of granule cells, whereas Caspase-3 may be involved in cell death of hippocampal CA1, CA3 and hilar neurons in the kainate epilepsy model. q 1999 Elsevier Science B.V. All rights reserved.