SELECTIVE UP-REGULATION OF PROTEIN-KINASE-C-EPSILON IN GRANULE CELLS AFTER KAINIC ACID-INDUCED SEIZURES IN RAT

Kainate-induced seizure activity causes persistent changes in the hipp ocampus that include synaptic reorganization and functional changes in the messy fibers. Using in situ hybridization histochemistry, the exp ression of PKC alpha, PKC beta, PKC gamma, PKC delta and PKC epsilon m RNAs was investigated in the hippocampus of adult rats following seizu res induced by a s.c. injection of kainic acid. In CA1 and CA3, we fou nd a significant decrease in PKC gamma mRNA 1 day after kainic acid wh ich persisted for a 2nd day in CA1. None of the other PKC isoform mRNA s were altered in CA1 or CA3. In granule cells, a significant up-regul ation specific to PKC epsilon mRNA was observed. One week after kainic acid administration, a marked increase in PKC epsilon immunoreactivit y was found that persisted 2 months after kainic acid administration. PKC epsilon immunoreactivity was found associated with messy fibers pr ojecting to the hilus of the dentate gyrus and to the stratum lucidum of the CA3 field and presumably with the newly sprouted messy fibers p rojecting to the supragranular layer. These data provide the first evi dence for a long-lasting increase of the PKC epsilon in the axons of g ranule cells caused by kainate-induced seizures and suggest that PKC e psilon may be involved in the functional and/or structural modificatio ns of granule cells that occur after limbic seizures. (C) 1997 Elsevie r Science B.V.