The stress protein response and its potential relationship to prolonged seizure activity

Recent investigations have shown that neuronal excitation can lead to a variety of changes in intracellular signaling that ultimately result in altered gene expression. In particular, the excessive neuronal activation seen with seizures leads to the induction of certain "immediate-early" genes that are transcription factors. These transcription factors presumably facilitate the subsequent expression of various "intermediate-late" or effector genes. Given the growing numbers of genes that appear to be modulated by seizures, it appears that seizures initiate a tremendous cascade of changes in gene expression over both the short and the long term. In this article, I discuss two main classes of gene products that are modulated by seizure activity: heat shock proteins and calcium binding proteins. By using both in vivo an in vitro systems, we and others are exploring the conditions that lead to altered expression of genes and the potential significance of such changes in expression. Although the functional meaning of the altered gene expression remains unknown, it seems likely that some of these changes will ultimately be related to certain components of neuronal vulnerability and epileptogenesis.