title: Experimental febrile seizures increase dendritic complexity of newborn dentate granule cells.
abstract: Febrile seizures (FS) are fever-associated convulsions, being the most common seizure disorder in early childhood. A subgroup of these children later develops epilepsy characterized by a hyperexcitable neuronal network in the hippocampus. Hippocampal excitability is regulated by the hippocampal dentate gyrus (DG) where postnatal neurogenesis occurs. Experimental FS increase the survival of newborn hippocampal dentate granule cells (DGCs), yet the significance of this neuronal subpopulation to the hippocampal network remains unclear. In the current study, we characterized the temporal maturation and structural integration of these post-FS born DGCs in the DG.
  
  
  
  Experimental FS were induced in 10-day-old rat pups. The next day, retroviral particles coding for enhanced green fluorescent protein (eGFP) were stereotactically injected in the DG to label newborn cells. Histochemical analyses of eGFP expressing DGCs were performed one, 4, and 8 weeks later and consisted of the following: (1) colocalization with neurodevelopmental markers doublecortin, calretinin, and the mature neuronal marker NeuN; (2) quantification of dendritic complexity; and (3) quantification of spine density and morphology.
  
  
  
  At neither time point were neurodevelopmental markers differently expressed between FS animals and normothermia (NT) controls. One week after treatment, DGCs from FS animals showed dendrites that were 66% longer than those from NT controls. At 4 and 8 weeks, Sholl analysis of the outer 83% of the molecular layer showed 20-25% more intersections in FS animals than in NT controls (p < 0.01). Although overall spine density was not affected, an increase in mushroom-type spines was observed after 8 weeks.
  
  
  
  Experimental FS increase dendritic complexity and the number of mushroom-type spines in post-FS born DGCs, demonstrating a more mature phenotype and suggesting increased incoming excitatory information. The consequences of this hyperconnectivity to signal processing in the DG and the output of the hippocampus remain to be studied.
authors.affiliation: Biomedical Research Institute BIOMED, Hasselt University, Hasselt, Belgium.|Department of Neurosurgery, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Raijmakers
authors.affiliation: Biomedical Research Institute BIOMED, Hasselt University, Hasselt, Belgium.
authors.forename: Elke
authors.initials: E
authors.lastname: Clynen
authors.affiliation: Biomedical Research Institute BIOMED, Hasselt University, Hasselt, Belgium.|Flemish Institute for Technological Research, Environmental Risk and Health Unit, Mol, Belgium.
authors.forename: Nick
authors.initials: N
authors.lastname: Smisdom
authors.affiliation: Biomedical Research Institute BIOMED, Hasselt University, Hasselt, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Nelissen
authors.affiliation: Biomedical Research Institute BIOMED, Hasselt University, Hasselt, Belgium.
authors.forename: Bert
authors.initials: B
authors.lastname: Brône
authors.affiliation: Biomedical Research Institute BIOMED, Hasselt University, Hasselt, Belgium.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rigo
authors.affiliation: Department of Neurosurgery, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Govert
authors.initials: G
authors.lastname: Hoogland
authors.affiliation: Biomedical Research Institute BIOMED, Hasselt University, Hasselt, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Swijsen
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D064032:Calbindin 2 / Q000378:metabolism; D003292:Convulsants / Q000633:toxicity; D003712:Dendrites / Q000502:physiology*; D018891:Dentate Gyrus / Q000254:growth & development / Q000473:pathology*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure*; D009479:Neuropeptides / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D019904:Polymethyl Methacrylate / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D003294:Seizures, Febrile / Q000139:chemically induced / Q000473:pathology*; D014161:Transduction, Genetic; D014162:Transfection
chemical_list: C576512:Calb2 protein, rat; D064032:Calbindin 2; D003292:Convulsants; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D049452:Green Fluorescent Proteins; D019904:Polymethyl Methacrylate; D010751:Phosphopyruvate Hydratase
keywords: Dendritogenesis; Dentate gyrus; Epileptogenesis; Hyperthermia; Neurogenesis; Spine density