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 thatis often associated with drug resistance. The current approach totreating patients with drug resistance involves surgery, which doesnot guarantee complete recovery. Currently, new antiepileptic drugsare being developed that target signaling cascades involved in epileptogenesis.The development of such drugs requires knowledge of the basic mechanisms ofepilepsy pathogenesis. The aim of this work was to investigate thedynamics of changes in proteins involved in the regulation of apoptosis,circadian rhythms and antioxidant response in the temporal cortexof the brain during prolonged kindling in the Krushinsky–Molodkina(KM) rat model of genetic audiogenic epilepsy. The dynamics of changesin proteins of interest—p53, CLOCK, Nrf2, p105—in the temporal cortexwere studied (immunohistochemistry assay, Western blotting). Itwas found that control KM rats had lower levels of p53 than Wistarrats. In KM rats exposed to kindling for 21 days, p53 level wasincreased compared to KM controls. CLOCK levels appeared to be downregulatedin the KM control group compared to the negative control and increasedin the 21-day kindling KM group compared to the 7-day kindling KMgroup. No changes in the production of Nrf2 and p105 were detected.The data obtained suggest that the changes in the levels of theinvestigated proteins in control KM rats compared to Wistar ratsare genetically determined. Induced epileptogenesis (kindling) for 21 daysleads to activation of the p53-dependent apoptosis pathway and possibledesynchronosis—alteration of circadian rhythms. The findings contributeto the study of temporal lobe epilepsy mechanisms and require furtherstudies related to mitochondrial apoptosis and sleep-wake cycleshift in the pathogenesis of temporal lobe epilepsy.