Prolonged expression of zinc finger immediate-early gene mRNAs and decreased protein synthesis following kainic acid induced seizures

In the present study in situ hybridization was used to study the effect of kainic acid induced seizures on the expression of the zinc finger immediate -early genes (IEGs) NGFI-A, NGFI-B, NGFI-C, egr-2, egr-3 and Nurr1. Kainic acid markedly induced these IEGs especially in hippocampus, cortex and amyg dala by 30 min. This induction gradually decreased and returned to baseline by 24 h in most regions. However, in the CA1 and CA3 subfields of hippocam pus known to be damaged by kainic acid the expression of all the IEGs excep t egr-2 remained elevated for 24 h. NGFI-A, NGFI-B, NGFI-C and to a lesser extent, Nurr1, remained elevated also in the subcortical region of the temp oral lobe. By 24 h incorporation of C-14-leucine decreased in the piriform cortex, amygdala, and in the CA1 and CA3 subfields, but not in CA2 and dent ate gyrus. These areas showing decreased protein synthesis in the hippocamp us by 24 h showed prolonged IEG induction, whereas IEG expression returned to control levels in areas showing normal protein synthesis. In the tempora l lobe decreased protein synthesis coexisted with decreased IEG expression, whereas areas in the vicinity of the region showing decreased protein synt hesis demonstrated elevated IEG expression. The decreased protein synthesis was localized in areas where extensive neuronal death has occurred. This p rolonged IEG induction in the hippocampus, which has been linked with neuro nal death, could solely represent a prolonged mRNA turnover caused by disru pted protein synthesis, The prolonged IEG expression in the temporal lobe a ppeared to be localized in regions where the cells are in stress, but still viable. The sustained IEG expression might therefore either represent a st ress response by which the neurons are trying to protect themselves or, alt ernatively, the IEG response may be an early sign indicating that these cel ls are initiating a pathway leading to programmed cell death.