Kainate-induced changes in gene expression in the rat hippocampus

This chapter focuses on the effects of kainate on the expression of opioid peptides and transcription factor genes. The molecular events that regulate gene expression are examined with an emphasis on the mechanisms that modulate the proenkephalin promotor activity. The opioid peptides expressed in the hippocampus include enkephalins and dynorphins. Both enkephalin- and dynorphin-related peptides are produced from precursor proteins. The 31 kDa proenkephalin is proteolyzed into five Metenkephalin and one Leu-enkephalin-containing peptides. Dynorphin A, dynorphin B (rimorphin), and α-neo-endorphin peptides are processed from the prodynorphin protein. These peptides are stored in synaptic vesicles and released by stimulation. Although their exact function is unknown, the opioid peptides are considered to be neuromodulators. Excitation of the hippocampal neuronal pathways by kainate administration increases opioid peptide gene expression and the release of opioid peptides. The amount of opioid peptide mRNA produced in the dentate gyrus is positively correlated with neuronal stimulation; prodynorphin increases several-fold within the first 3 h after kainate treatment and declines to near basal levels after 24 h. The levels of the proenkephalin message peak at 6 h after kainate injection and are still elevated 2–3-fold 48 h later.