Molecular neurobiological approach to the pathogenesis of epilepsy: a preliminary study

We studied the effects and the interactions of some candidate genes related to the pathogenesis of epilepsy using a domestic audiogenic epilepsy-prone rat, matched with the epilepsy-resistant Wistar rat, and primary fetal cerebral cortical neuronal cell cultures of both. The preliminary results showed that there was a possible abnormality of the CCK gene at the post-translational stage in the early postnatal period in P77PMC rat brain; the later rapidly increased rate of CCK-8 synthesis in the hippocampus and subcortical region may represent a compensatory response to the neuronal pathways involved in audiogenic seizures. CCK-8 can decrease the NMDA (1 microM)-induced free intracellular Ca2+ concentration, so it seems to be an inhibitory neuromodulator. In neuronal cell cultures, the NMDA (0.1 microM)-induced c-fos mRNA expression on culture day 18 in vitro was higher in P77PMC than Wistar rats (P < 0.05). Interleukin-1 (20 nM) can induce endogenous opioid mRNA expression and peptide release in neuronal cell cultures, which can be abolished by the addition of antisense oligos of c-fos/c-jun to cell cultures treated with interleukin-1. Both interleukin-1 and opioids can increase the free intracellular Ca2+ concentration, and their specific antagonists can reverse their effects, so they both seem to be excitatory neuromodulators in the CNS.