Long-lasting enhancement of GABA(A) receptor expression in newborn dentate granule cells after early-life febrile seizures

Ann Swijsen, Bert Brone, Jean-Michel Rigo*, Govert Hoogland

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Web of Science)

Abstract

Febrile seizures (FS) are the most common type of seizures in childhood and are suggested to play a role in the development of temporal lobe epilepsy (TLE). Animal studies demonstrated that experimental FS induce a long-lasting change in hippocampal excitability, resulting in enhanced seizure susceptibility. Hippocampal neurogenesis and altered ion channel expression have both been proposed as mechanisms underlying this decreased seizure threshold. The present study aimed to analyze whether dentate gyrus (DG) cells that were born after FS and matured for 8 weeks display an altered repertoire of ligand-gated ion channels. To this end, we applied an established model, in which FS are elicited in 10-day-old rat pups by hyperthermia (HT). Normothermia littermates served as controls. From postnatal day 11 (P11) to P16, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells immediately following FS. At P66, we evaluated BrdU-labeled DG cells for coexpression with gamma-aminobutyric acid-type A receptors (GABA(A)Rs) and N-methyl-D-aspartate receptors (NMDARs). In control animals, 40% of BrdU-labeled cells coexpressed GABA(A)R beta 2/3, whereas in rats that had experienced FS, 60% of BrdU-labeled cells also expressed GABA(A)R beta 2/3. The number of BrdU-NMDAR NR2A/B coexpressing cells was in both groups about 80% of BrdU-labeled cells. The results demonstrate that developmental seizures cause a long-term increase in GABA(A)R beta 2/3 expression in newborn DG cells. This may affect hippocampal physiology.
Original languageEnglish
Pages (from-to)1516-1527
JournalDevelopmental neurobiology
Volume72
Issue number12
DOIs
Publication statusPublished - Dec 2012

Keywords

  • febrile seizures
  • neurogenesis
  • gamma-aminobutyric acid type A receptor
  • N-methyl-D-aspartate receptor
  • dentate gyrus

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