KAINIC ACID MODEL OF TEMPORAL LOBE EPILEPSY: NANOSCALE OSCILLATIONS OF HIPPOCAMPAL MITOCHONDRIA

Mitochondrial dysfunction is increasingly recognized as a central component of epileptogenesis, yet sensitive biophysical markers capable of capturing early mitochondrial alterations remain limited. Kainic acid (KA) model of temporal lobe epilepsy (TLE) is one of the most reliable tools for understanding the mechanisms of epileptogenesis and induces behavioral, electro-physiological, chemical and histological effects that are similar to those observed in patients with TLE. In the present study, we evaluate the nanoscale oscillatory behavior of mitochondria isolated from primary hippocampal neurons, analyzed using optical nanomotion detection (ONMD) technique with single-organelle sensitivity to reveal 2D displacement of isolates. Mitochondria were exposed of two concentrations of KA (0.5 and 1 μM) for varying incubation periods. Our data showed that, exposure to 0.5 μM KA induced modest, non-significant changes, while treatment with 1 μM KA resulted in a pronounced and statistically significant increase in mitochondrial nanomotion, most prominently after 90 minutes of incubation. Replication experiments confirmed the temporal specificity of this response. In contrast, nanomotion analysis of whole intact hippocampal neurons treated with 1 μM KA revealed no significant changes, indicating that KA-induced mitochondrial nanomotion alterations are not directly reflected at the cellular level. The character of oscillations depends on the concentration of KA and the duration of KA action. The present study is the preliminary research where the effect of epilepsy-produced drug on the nanomotion of particular mitochondria is described. The data indicate that 1 μM KA is able to affect subtle nanomotion of mitochondria and optical nonemotion detection system can detect such changes.