The role of bcl-2 family of genes during kindling

Purpose: Several experimental models of human temporal lobe epilepsy have shown that apoptotic death of neurons is an important part of this degenerative disease. However, the role of apoptotic regulators is not clear during the epileptogenesis. Therefore we investigated the expression pattern of bcl-2 family of genes during the formation of kindling model of epilepsy in rats.Methods: We examined the expression pattern of bax, bcl-2, bcl-x(L), mtd, and bcl-w, both at messenger RNA (mRNA) and protein level in the brain tissues during the formation of epilepsy with kindling model in adult rats, which has been the most acceptable form of experimental model of human epilepsy. We also assessed the onset of DNA fragmentation by using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay.Results: Animals have started to have epileptic discharges after day 10 of kindling model. Recurrent subthreshold electrical stimuli induced not only epileptic foci but also the expression of bax, an inducer of apoptosis, in this time period. Conversely, bcl-x(L), which is an inhibitor of apoptosis, had an opposite pattern of expression both at mRNA and protein level during the formation of epilepsy. We did not observe DNA fragmentation by TUNEL staining.Conclusions: Our study shows differential expression of Bax and Bcl-x(L) at the CA1 region during the formation of hippocampal kindling model. The absence of DNA fragmentation during this period suggests that epileptic changes in neurons have the potential to induce DNA fragmentation by altering the expression levels of Bax and Bcl-x(L).C1 Bilkent Univ, Dept Mol Biol & Genet, TR-06800 Ankara, Turkey.Pamukkale Univ, Dept Physiol, Denizli, Turkey.Pamukkale Univ, Dept Neurol, Denizli, Turkey