NOVEL DIFFERENTIALLY EXPRESSED GENES INDUCED BY KAINIC ACID IN HIPPOCAMPUS - PUTATIVE MOLECULAR EFFECTORS OF PLASTICITY AND INJURY

Systemic kainic acid administration in rats induces acute limbic statu s epilepticus and subsequent neuronal degeneration and development of chronic hyperexcitability with similarities to human temporal lobe epi lepsy, The mechanisms mediating the responses to kainic acid likely in volve transcriptional changes in genes of importance for cellular inju ry, protection, and plasticity. We have used an arbitrarily primed PCR technique to identify such changes in the rat dentate gyrus, Three pr eviously uncharacterized transcripts were found to be upregulated in t he dentate gyrus 4 h following systemic kainic acid. In situ hybridiza tion using riboprobes transcribed from the cloned PCR fragments were u sed to confirm differential expression specifically in dentate granule neurons following seizure. Basal expression for all three transcripts is widespread throughout the rat brain, with the highest levels seen in the hippocampal pyramidal and granule cell layers. The novel sequen ces do not match any known full-length cDNAs and may belong to novel g ene families. However, they all showed high homology to human partial cDNA sequences (ESTs) that are expressed in brain as well as several o ther tissues. Two additional transcripts identified in this study corr oborate earlier findings on differential expression of heat-shock prot eins after seizure. The navel transcripts found in this study may be i nvolved in epileptogenesis and neuronal responses to damage following seizure. (C) 1997 Academic Press.