Пифитрин-альфа тормозит дифференцировку вновь образованных клеток субгранулярной зоны зубчатой извилины у крыс линии Крушинского–Молодкиной при аудиогенном киндлинге

Abstract

One of the main goal of modern neurobiology is search for approaches to prevent structural violations in the brain. In particular, damage to the hippocampus after epileptic activity. Epilepsy leads to an increase in proliferation in the hippocampal neurogenic niche - subgranular cells layer of dental gyrus. In recent years, there is a prevalent idea that new-born cells contribute to epileptogenesis to a greater extent than prevent neurodegenerative damage. We suggested that proapoptotic protein p53 can be one of possible therapeutic targets for epilepsy and neurodegenerative consequences of this disease.In present work, we used The Krushinsky - Molodkina (KM) inbred rat strain. This strain is genetically prone to audiogenic seizures (AGS). Audiogenic kindling induced epileptiform activity in the limbic system and the cortex. It has been shown that in initial stages of epileptogenesis 4 AGS lead to increase in proliferation, aberrant migration in hilus and acceleration of differentiation of newborn cells. We did not show any disturbance in apoptosis nor autophagy in early development of limbic epilepsy. Pifitrin-α (chemical inhibitor of p53) did not lead to changes in apoptosis and autophagy but caused increase in proliferation and migration of newborn cells in granular cell layer and hilus of dental gyrus. However, in a week after the last seizure the number of differentiated cells decreased despite a significant increase in the number of newborn cells in the group with inactivation of p53 compared to the vehicle control group. Decreased number of differentiated cells tells that pifitrin -α may be used as a potential therapeutic agent for reduction in neurodegeneration which is associated with epilepsy.