Abstracts

Rationale: Epilepsy is a neurological condition that affects approximately 50 million people worldwide and is characterised by recurrent spontaneous seizures. To date, non-invasive biomarkers of epilepsy and treatment response are lacking. Telomeres are repeating non-coding DNA sequences located at the end of linear eukaryotic chromosomes which protect chromosomes by preventing their degradation during DNA replication. Recent studies have associated shortened telomere length with aging and neurological conditions including traumatic brain injury and Alzheimer’s disease. However, the relationship between telomere length and epilepsy is unknown. The current study assessed telomere length in a rat model of temporal lobe epilepsy (TLE) treated with or without antiepileptic agents. Methods: Eleven-week old Wistar rats underwent kainic acid induced-status epilepticus (SE) for four hours. Nine weeks post-SE, rats were implanted with EEG recording electrodes and video-EEG was recorded for one week. Post-SE rats that did not have a spontaneous seizure at this time were excluded from the study. After this initial EEG recording period, rats were randomly assigned to one of four treatment groups delivered through osmotic pumps for four weeks: post-SE + sodium selenate (1 mg/kg/day, n=8); post-SE + levetiracetam (200 mg/kg/day, n=10); post-SE + vehicle (n=6); sham + vehicle (n=9). Animals underwent a second period of EEG recordings 8 weeks after the last day of treatment. 24 weeks after the induction of SE, skin cells (via ear notch) and blood were collected and DNA was extracted to determine telomere length via PCR. Results: Following drug washout, post-SE animals treated with sodium selenate had fewer seizures (p< 0.05) per day when compared to vehicle-treated animals. Notably, post-SE rats treated with vehicle had significantly shorter telomeres than sham-controls (p< 0.05). Post-SE rats treated with selenate had significantly longer telomeres than their vehicle-treated counterparts (p< 0.05), and did not significantly differ from the sham controls. Levetiracetam treated post-SE rats had non-significant trends suggesting both fewer seizures and longer telomeres than the post-SE vehicle-treated rats. Conclusions: This novel study found that rats with chronic epilepsy had reduced telomere length relative to sham controls. Furthermore, epileptic rats treated with sodium selenate had fewer seizures and longer telomeres compared to the vehicle-treated epileptic rats suggesting that sodium selenate has a disease modifying effect. Overall, these findings suggest that telomere length may represent a useful non-invasive biomarker for temporal lobe epilepsy, which may also be used to assess efficacy of medical and surgical treatments. We are currently conducting telomere analysis studies in patients with temporal lobe epilepsy. Funding: Melbourne Early Career Research Scholarship