Abstracts

Febrile seizures (FS) are early-life seizures thought to play a role in epileptogenesis. By labeling cells that are dividing immediately following experimental FS, we previously demonstrated that at eight weeks post-seizure there were significantly more dentate granule cells (DGCs) left in male seizure rats than in controls (Lemmens et al. Epilepsia 2005, 46(10):1603-1612). The purpose of the present study was to determine the phenotype of these newborn cells., On postnatal day (PN) 10, hyperthermia-induced seizures (HT, [plusmn] 42[deg]C core temperature) were evoked in Sprague-Dawley rats by exposure to a regulated stream of heated air. Littermates were used as normothermia controls (NT, [plusmn] 35[deg]C core temperature). From PN11 to PN16, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. At PN66, we counted the number of BrdU-labeled DGCs that colocalized with the neuronal marker NeuN, astroglial marker glial fibrillary acidic protein (GFAP), neuronal excitatory amino acid transporter 3 (EAAT3), GABAergic neuronal marker glutamic acid decarboxylase 67 (GAD67) or microglial marker tomato lectin (TL)., At PN66, rats that had displayed behavioral seizures in response to HT treatment (HT+FS) had 20-25% more BrdU-labeled DGCs than NT controls or HT-treated rats that did not display behavioral seizures (HT-FS). In all rats, almost all BrdU-labeled DGCs colocalized with NeuN, and rarely with GFAP, GAD67, or TL. In NT controls and HT-FS rats 22% of BrdU-labeled DGCs colocalized with EAAT3, in contrast to only 14% in HT+FS rats., Early-life seizures decrease the population of newborn DGCs that survive and mature into EAAT3-positive neurons and do not affect the GABAergic DGC population. This may affect hippocampal physiology in young adulthood., (Supported by the Dutch Brain Foundation (grant H00.03 to GH) and by a Marie Curie Fellowship of the European Community program [quot]Quality of Life and Management of Living Resources[quot] under contract number QLK6-CT-2000-60042 and reference number QLK6-GH-00-60042-42.)