Abstracts

Rationale: Febrile seizures (FS) are the most common type of seizures in children, affecting 4% of infants between the age of 3 months and 5 years. Retrospective studies indicate that adult patients with hippocampal sclerosis-associated temporal lobe epilepsy have a 40% incidence of FS, suggesting a causal relationship. Preclinical research suggests that FS persistently increase hippocampal excitability, resulting in enhanced seizure susceptibility. Based on these findings, it is hypothesized that FS change the expression and/or properties of neuronal ion channels. A possible mechanism to achieve this changed neuronal ion channel functioning is by neurogenesis. Aim: To analyze the long-term impact of FS on hippocampal dentate granule cell functioning of cells that are born immediately after these seizures. Methods: In an established model, FS are induced in 10-day old rat pups by exposing them for 30 min to heated air. Control pups undergo a normothermia treatment and do not display behavioral seizures. One to eight weeks later, neurogenesis was studied by bromodeoxyuridine (BrdU) immunohistochemistry and responses to GABA were recorded in dentate granule cells by whole-cell patch-clamp technique. Results: Eight weeks after treatment, FS animals exhibit 25% more BrdU-positive granule cells. Though more than 90% of these cells mature in adult neurons (i.e. co-localize with NeuN), they have differentiated in a different phenotype (i.e. less cells express glutamate transporters (EAAT3) and more cells express GABAAβ2,3). One week after treatment, GABAA receptors from FS animals are two-times more sensitive to GABA. Conclusions: These data support the hypothesis that FS persistently alter the neuronal excitability.