MOLECULAR NEUROBIOLOGICAL APPROACH TO THE PATHOGENESIS OF EPILEPSY - A PRELIMINARY-STUDY

We studied the effects and the interactions of some candidate genes re lated to the pathogenesis of epilepsy using a domestic audiogenic epil epsy-prone rat, matched with the epilepsy-resistant Wistar rat, and pr imary fetal cerebral cortical neuronal cell cultures of both. The prel iminary results showed that there was a possible abnormality of the CC K gene at the post-translational stage in the early postnatal period i n P77PMC rat brain; the later rapidly increased rate of CCK-8 synthesi s in the hippocampus and subcortical region may represent a compensato ry response to the neuronal pathways involved in audiogenic seizures. CCK-8 can decrease the NMDA (1 mu M)-induced free intracellular Ca2+ c oncentration, so it seems to be an inhibitory neuromodulator. In neuro nal cell cultures, the NMDA (0.1 mu M)-induced c-fos mRNA expression o n culture day 18 in vitro was higher in P77PMC than Wistar rats (P < 0 .05). Interleukin-1 (20 nM) can induce endogenous opioid mRNA expressi on and peptide release in neuronal cell cultures, which can be abolish ed by the addition of antisense oligos of c-fos/c-jun to cell cultures treated with interleukin-l. Both interleukin-l and opioids can increa se the free intracellular Ca2+ concentration, and their specific antag onists can reverse their effects, so they both seem to be excitatory n euromodulators in the CNS.