Novel Differentially Expressed Genes Induced by Kainic Acid in Hippocampus: Putative Molecular Effectors of Plasticity and Injury

Abstract

Systemic kainic acid administration in rats induces acute limbicstatus epilepticusand subsequent neuronal degeneration and development of chronic hyperexcitability with similarities to human temporal lobe epilepsy. The mechanisms mediating the responses to kainic acid likely involve transcriptional changes in genes of importance for cellular injury, protection, and plasticity. We have used an arbitrarily primed PCR technique to identify such changes in the rat dentate gyrus. Three previously uncharacterized transcripts were found to be upregulated in the dentate gyrus 4 h following systemic kainic acid.In situhybridization using riboprobes transcribed from the cloned PCR fragments were used 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 sequences do not match any known full-length cDNAs and may belong to novel gene families. However, they all showed high homology to human partial cDNA sequences (ESTs) that are expressed in brain as well as several other tissues. Two additional transcripts identified in this study corroborate earlier findings on differential expression of heat-shock proteins after seizure. The novel transcripts found in this study may be involved in epileptogenesis and neuronal responses to damage following seizure.