title: Long-lasting enhancement of GABA(A)  receptor expression in newborn dentate granule cells after early-life febrile seizures.
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 γ-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 β2/3, whereas in rats that had experienced FS, 60% of BrdU-labeled cells also expressed GABA(A)R β2/3. 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 β2/3 expression in newborn DG cells. This may affect hippocampal physiology.
authors.affiliation: Research Group Cell Physiology, BIOMED Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Swijsen
authors.forename: Bert
authors.initials: B
authors.lastname: Brône
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rigo
authors.forename: Govert
authors.initials: G
authors.lastname: Hoogland
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018891:Dentate Gyrus / Q000378:metabolism*; D004195:Disease Models, Animal; D005334:Fever / Q000150:complications / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D008297:Male; D018613:Microscopy, Confocal; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000096:biosynthesis*; D003294:Seizures, Febrile / Q000378:metabolism*
chemical_list: D011963:Receptors, GABA-A