title: 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% of Western-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 convulsion-susceptible 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.
authors.affiliation: Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Bart C
authors.initials: BC
authors.lastname: Jongbloets
authors.affiliation: Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Koen L I
authors.initials: KL
authors.lastname: van Gassen
authors.affiliation: Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Anne A
authors.initials: AA
authors.lastname: Kan
authors.affiliation: Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Anneke H O
authors.initials: AH
authors.lastname: Olde Engberink
authors.affiliation: Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Marina
authors.initials: M
authors.lastname: de Wit
authors.affiliation: Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Inge G
authors.initials: IG
authors.lastname: Wolterink-Donselaar
authors.affiliation: Molecular Cancer Research, Division Biomedical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Marian J A
authors.initials: MJ
authors.lastname: Groot Koerkamp
authors.affiliation: Brain Center Rudolf Magnus, Department of Pediatric Neurology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Onno
authors.initials: O
authors.lastname: van Nieuwenhuizen
authors.affiliation: Molecular Cancer Research, Division Biomedical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Frank C P
authors.initials: FC
authors.lastname: Holstege
authors.affiliation: Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Pierre N E
authors.initials: PN
authors.lastname: de Graan
mesh_terms: D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism* / Q000473:pathology; D056654:CA3 Region, Hippocampal / Q000378:metabolism* / Q000473:pathology; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D063990:Gene Ontology; D018869:Heat-Shock Response; D008297:Male; D008810:Mice, Inbred C57BL; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D003294:Seizures, Febrile / Q000378:metabolism* / Q000473:pathology; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D016900:Neurofilament Proteins; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571338:Cnp protein, mouse