Dynamics of Changes in Markers of Apoptosis, Circadian Rhythms and Antioxidant Processes in the Model of Temporal Lobe Epilepsy in Rats

Temporal lobe epilepsy is a common neurological disorder that is often associated with drug resistance. The current approach to treating patients with drug resistance involves surgery, which does not guarantee complete recovery. Currently, new antiepileptic drugs are being developed that target signaling cascades involved in epileptogenesis. The development of such drugs requires knowledge of the basic mechanisms of epilepsy pathogenesis. The aim of this work was to investigate the dynamics of changes in proteins involved in the regulation of apoptosis, circadian rhythms and antioxidant response in the temporal cortex of the brain during prolonged kindling in the Krushinsky–Molodkina (KM) rat model of genetic audiogenic epilepsy. The dynamics of changes in proteins of interest—p53, CLOCK, Nrf2, p105—in the temporal cortex were studied (immunohistochemistry assay, Western blotting). It was found that control KM rats had lower levels of p53 than Wistar rats. In KM rats exposed to kindling for 21 days, p53 level was increased compared to KM controls. CLOCK levels appeared to be downregulated in the KM control group compared to the negative control and increased in the 21-day kindling KM group compared to the 7-day kindling KM group. No changes in the production of Nrf2 and p105 were detected. The data obtained suggest that the changes in the levels of the investigated proteins in control KM rats compared to Wistar rats are genetically determined. Induced epileptogenesis (kindling) for 21 days leads to activation of the p53-dependent apoptosis pathway and possible desynchronosis—alteration of circadian rhythms. The findings contribute to the study of temporal lobe epilepsy mechanisms and require further studies related to mitochondrial apoptosis and sleep-wake cycle shift in the pathogenesis of temporal lobe epilepsy.