Abstracts

Rationale: Inflammation may be a fundamental mechanism of ictogenesis and epileptogenesis. A leukotriene receptor (CysLT-R) antagonist exerts anticonvulsant effect in patients with epilepsy and rodent models as well. To study the anticonvulsant mechanism that a CysLT-R antagonist plays, we used DNA arrays of the hippocampal gene expression in rats fed a CysLT-R antagonist. Methods: Male Sprague-Dawley rats were fed CE-2 (CE 2 group) or CE-2 containing 0.6% (w/w) pranlukast (PL) that antagonizes CysLT1and 2-R and is used human allergy. Experimental rats were fed with PL 2 for days or 2 weeks (P2D group and P2W group). At the end of PL treatment, rats in all groups were stimulated with alternating current of 70 V for 3 sec through the pinna, to evoke maximal electroshock (MES). We measured the duration of tonic flexion, tonic extension, clonic convulsions of MES. Rats by group were sacrificed mRNA extracted from the hippocampus. Changes in gene expression of mRNA were examined by DNA array tips and analyzed by Ingenuity Pathway Analysis (IPA). Results: P2W animals had significantly shorter duration of seizures than the CE2 group. However there was no difference between P2D and CE2 animals. Total genes with a two-fold increase or 50% decrease was >3,000 in P2W rats compared with CE2 group rats, however is the group P2D those genes significantly changed was < 1,000. From network functions shown by the IPA analysis, there were numerous network functions found in P2W animals. Functions influenced by pranlukast administration (P2W group ) "Cell-To-Cell Signaling and Interaction, Cellular Growth and Proliferation, DNA Replication, Recombination, and Repair". The P2D control group did not have significant DNA changes. Conclusions: We found that many genes appear to be associated with the inhibitory effect of PL on MES. Chronic administration had an effect, but not acute treatment. Our finding suggests that long-duration of administration of PL needs to be evaluated in other models of epilepsy. CysLT1&2R antagonists used to treat allergy in humans, along with studies of gene expression of CysLT1 antagonist montelukast in rat hippocampus need further study as anticonvulsants and even antiepileptogenic agents. Funding: There is no funding in this study.