Expression profiling after prolonged experimental febrile seizures in mice suggests structural remodeling in the hippocampus

Abstract

Febrile seizures are the most prevalent type of seizures among children up to 5 years of age (2-4% ofWestern-European children). Complex febrile seizures are associated with an increased risk to develop temporal lobe epilepsy. To investigate short-and long-Term effects of experimental febrile seizures (eFS), we induced eFS in highly febrile convulsionsusceptible C57BL/6J mice at post-natal day 10 by exposure to hyperthermia (HT) and compared them to normotherm-exposed (NT) mice.We detected structural re-organization in the hippocampus 14 days after eFS. To identify molecular candidates, which entrain this structural re-organization, we investigated temporal changes in mRNA expression profiles eFS 1 hour to 56 days after eFS.We identified 931 regulated genes and profiled several candidates using in situ hybridization and histology at 3 and 14 days after eFS. This is the first study to report genome-wide transcriptome analysis after eFS in mice.We identify temporal regulation of multiple processes, such as stress-, immune-and inflammatory responses, glia activation, glutamate-glutamine cycle and myelination. Identification of the short-and long-Term changes after eFS is important to elucidate the mechanisms contributing to epileptogenesis.