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Epilepsia
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Epilepsia
Article . 2016 . Peer-reviewed
License: Wiley Online Library User Agreement
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Experimental febrile seizures increase dendritic complexity of newborn dentate granule cells

Authors: RAIJMAKERS, Marjolein; CLYNEN, Elke; SMISDOM, Nick; NELISSEN, Sofie; BRONE, Bert; RIGO, Jean-Michel; HOOGLAND, Govert; +1 Authors

Experimental febrile seizures increase dendritic complexity of newborn dentate granule cells

Abstract

SummaryObjectiveFebrile 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.MethodsExperimental 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.ResultsAt 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.SignificanceExperimental 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.

Countries
Belgium, Netherlands
Keywords

Doublecortin Domain Proteins, Male, Doublecortin Protein, Neurogenesis, Green Fluorescent Proteins, Convulsants, Animals, Humans, Polymethyl Methacrylate, Dentate gyrus, Hyperthermia, Spine density, Neurons, Neuropeptides, Age Factors, Dendritogenesis, Dendrites, Epileptogenesis, Rats, Disease Models, Animal, HEK293 Cells, Animals, Newborn, Calbindin 2, Phosphopyruvate Hydratase, Dentate Gyrus, Microtubule-Associated Proteins, Dendritogenesis; Dentate gyrus; Epileptogenesis; Hyperthermia; Neurogenesis; Spine density

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    influence
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
24
Top 10%
Average
Top 10%
bronze