ISOZYME SPECIFIC CHANGES IN THE EXPRESSION OF PROTEIN-KINASE-C ISOZYME (ALPHA-ZETA) GENES IN THE HIPPOCAMPUS OF RATS INDUCED BY KINDLING EPILEPTOGENESIS

The transcript levels of the protein kinase C (PKC) isoform genes duri ng the development of a kindled epileptogenic focus, elicited by stimu lation of Schaffer collateral/commissural fibres in the CA1 area of th e rat hippocampus, were compared with the expression levels in control animals using a semi-quantitative in situ hybridization approach. In the hippocampus of control animals, the levels of PKC-alpha-zeta trans cripts showed a gene-specific expression pattern and significant diffe rences in expression level were observed between the neurons of CA1, C A3 and fascia dentata. In the early stages of kindling epileptogenesis , i.e. following 6 and 14 afterdischarges, specific changes in the exp ression levels of PKC-beta, -epsilon, and -zeta but not of PKC-beta, - gamma, and -delta were found. PKC-beta expression was decreased in CA1 , while the PKC-epsilon and -zeta specific hybridization signals were increased in CA1, CA3 and fascia dentata. In fully kindled animals, th at had experienced 10 generalized seizures, most expression levels ten ded to return to control values. One month after the last seizure no s ignificant alterations were encountered. These results indicate an inv olvement of specific PKC-isoform gene expression in the induction of a n epileptogenic focus, but not in the maintenance of the long-lasting kindled state.