Impaired postnatal development of the hippocampus of Krushinsky-Molodkina rats genetically prone to audiogenic seizures

Abstract

The hippocampus plays an important role in epilepsy progression even if it is not involved in seizure generalization. We hypothesized that abnormal development of the hippocampus may underlie epileptogenesis. Here we analyzed postnatal development of the hippocampus of Krushinsky-Molodkina (KM) rats, which are the animal model of reflex audiogenic epilepsy. KM rats are genetically prone to audiogenic seizures that are expressed in age-dependent manner. The study was performed on seizure-naïve KM rats at several days of postnatal development (P15, P30, P60, P120). Wistar rats of the corresponding ages were used as a control. We showed that at early stages (P15, P30), the hippocampus of KM rats was characterized by significantly smaller cell population, but the number of proliferated cells was increased in comparison with control Wistar rats. Only at P60 proliferation and the total number of the hippocampal cells reached a level equal to Wistar rats. These data suggest delayed postnatal development of the hippocampus of KM rats. Analysis of apoptosis demonstrated significantly increased number of TUNEL-positive cells in the dentate gyrus (DG) of KM rats at P30 that was accompanied with expression of p53, Bcl-2 and cleaved caspases 3 and 9. Additionally, at all analyzed stages in the hilus of KM rats, the number of new-born glutamatergic cells was significantly increased that suggests formation of hilar ectopic granular cells. Our data suggest that in the case of hereditary epilepsy aberrant neurogenesis may be genetically determined.

Keywords: Apoptosis; Audiogenic seizures; Autophagy; Hippocampus; Krushinsky-Molodkina rats; Postnatal ontogenesis; Proliferation.