Cytogenesis in the dentate gyrus after neonatal hyperthermia-induced seizures: What becomes of surviving cells?

Abstract

Purpose: Febrile seizures (FS) are early-life seizures thought to play a role in epileptogenesis. By labeling cells that were dividing immediately following experimental FS, we previously demonstrated that significantly more of these newborn cells in the dentate gyrus (DG) survived 8 weeks later, relative to animals that did not experience FS. The purpose of the present study was to determine the long-term fate of these newborn cells. Methods: On postnatal day (PN) 10, hyperthermia-induced seizures (HT, +/- 42 degrees C core temperature) were evoked in Sprague-Dawley rats and littermates were used as normothermia controls (NT, +/- 35 degrees C core temperature). From PN11 to PN16, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. At PN66, we evaluated the number of BrdU-labeled cells in the DG that colocalized with the neuronal marker NeuN, glial marker glial fibrillary acidic protein (GFAP), neuronal excitatory amino acid transporter 3 (EAAT3), GABAergic neuronal marker glutamic acid decarboxylase 67 (GAD67) or microglia marker tomato lectin (TL). Results: In all rats, almost all BrdU-labeled cells in the DG, that showed double-labeling, colocalized with NeuN, and rarely with GFAP, GAD67, or TL. In NT controls and HT rats that did not experience seizures ("HT-no seizures"), similar to 23% of BrdU-labeled cells colocalized with EAAT3, which was significantly different from 14% in HT rats that did experience seizures (HT + FS). Discussion: Early-life seizures decrease the population of newborn cells that survive and mature into EAAT3-positive neurons and do not affect the GABAergic cell population. This may affect hippocampal physiology in young adulthood.