Analysis of Neural Stem Cells from Krushinskii–Molodkina Rats, Which Have a Genetic Predisposition to Audiogenic Seizures

Abstract

Epilepsy is known to be associated with impairment to neurogenesis processes. Studies have identified a number of genes whose mutations are liked with the development of inherited forms of epilepsy, and some of these genes are involved in controlling the proliferation and differentiation of neural stem cells (NSC). These data led us to the hypothesis that the development of aberrant neurogenesis may be genetically determined and is the cause of the development of epilepsy driven by genetic etiology. This study was performed in vitro on NSC isolated from the hippocampus of Krushinskii–Molodkina (KM) rats on days 14–17 of postnatal development. Rats of the inbred strain KM, which were bred from the Wistar strain, are genetically predisposed to audiogenic seizures and provide a model of audiogenic epilepsy. Controls consisted of NSC from the hippocampus of Wistar rats. Cell cultures were incubated for 10 days in medium containing retinoic acid to stimulate differentiation. Levels of NSC proliferation were assessed by supplementing the medium with bromodeoxyuridine (BrdU). These results showed that the level of NSC proliferation in KM rats was significantly lower than that in Wistar rats and that KM NSC differentiated more quickly. Analysis of the directions of differentiation showed that NSC from KM rats differentiated predominantly into glutamatergic and catecholaminergic neurons. These data provide evidence that an increased level of maturation of glutamatergic neurons in the hippocampus of KM rats is genetically determined and may be one of the main factors responsible for the development of epileptiform activity in these rats.