Different effects of mild and severe seizures on hippocampal neurogenesis in adult rats

Abstract

Recent evidence shows that functional neurogenesis exists in the adult hippocampus and that epileptic seizures can increase neurogenesis in the dentate gyrus (DG). However, it is unknown whether different seizure severity has different effects on neurogenesis in the DG of adult rats. In this study, we examined hippocampal neurogenesis in the rat mild and severe seizure preparations characterized with frequent wet dog shakes and severe status epilepticus, respectively. Both mild and severe seizures promoted the mitotic activity in the DG, but severe seizures caused a stronger cell proliferative response than mild seizures. Less than 20% of newborn cells in the DG differentiated into neurons in rats suffering severe seizures, whereas more than 60% of newborn dentate cells differentiated into neurons in control and mild seizure groups. Most newborn neurons migrated into the granular cell layer in control and mild seizure groups, but severe seizures were associated with an aberrant migration of newborn neurons into the dentate hilus. Severe seizures induced astrocyte activation and the expression of nestin and the migration directional molecules netrin 1 and Sema-3A in the hilus, which were not present in the hilus of control and mild seizure-attacked rats, suggesting that these molecules are involved in the aberrant migration of newborn neurons.