Biphasic response of hippocampal dynorphin expression following recurrent limbic seizure

The opioid peptide dynorphin (DYN) is expressed normally at high levels in dentate gyrus granule cells in hippocampus and in neurons in entorhinal and neocortex. In the present study, ribonuclease protection and in situ hybridization analyses were used to examine preproDYN mRNA expression in hippocampus and neocortex following recurrent limbic seizure induced by a unilateral electrolytic lesion of the dentate gyrus hilus. In this paradigm, electrographic seizures within hippocampus recur intermittently from 1.6 to 12 h following the hilus lesion (HL). Solution hybridization-ribonuclease protection analysis of preproDYN mRNA levels in hippocampal dentate gyrus/CA1 samples from rats sacrificed 6 and 12 h following HL revealed an approximate 6-fold increase above control values at both times. PreproDYN mRNA levels returned toward control values by 24 h post-HL, were suppressed up to 10-fold below control values at 48 and 96 h post-HL, and then returned to control levels by 10 days post-HL. In situ hybridization analyses confirmed the biphasic nature of seizure-induced changes in preproDYN expression specifically within dentate gyrus granule cells. Additionally, these latter studies demonstrated that seizures induce expression of preproDYN mRNA in a small population of neurons within stratum pyramidale CAL Transient increases in preproDYN mRNA were also detected in subiculum and entorhinal cortex. However, in neocortex hybridization of preproDYN mRNA remained constant through 96 h post-HL. These findings of biphasic seizure-induced alterations in preproDYN mRNA expression can be contrasted with previously described changes in gene expression following limbic seizure activity and suggest that different cellular mechanisms regulate expression of colocalized hippocampal neuropeptides such as dynorphin, Metenkephalin, and neuropeptide Y.