Cytogenesis in the dentate gyrus after neonatal hyperthermia-induced seizures: what becomes of surviving cells?
OBJECTIVE
Febrile seizures (FS) are early-life seizures thought to play a role in epileptogenesis. By labeling cells that were dividing immediately following experimental FS, we previously demonstrated that significantly more of these newborn cells in the dentate gyrus (DG) survived 8 weeks later, relative to animals that did not experience FS. The purpose of the present study was to determine the long-term fate of these newborn cells.


METHODS
On postnatal day (PN) 10, hyperthermia-induced seizures (HT, +/-42 degrees C core temperature) were evoked in Sprague-Dawley rats and littermates were used as normothermia controls (NT, +/-35 degrees C core temperature). From PN11 to PN16, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. At PN66, we evaluated the number of BrdU-labeled cells in the DG that colocalized with the neuronal marker NeuN, glial marker glial fibrillary acidic protein (GFAP), neuronal excitatory amino acid transporter 3 (EAAT3), GABAergic neuronal marker glutamic acid decarboxylase 67 (GAD67) or microglia marker tomato lectin (TL).


RESULTS
In all rats, almost all BrdU-labeled cells in the DG, that showed double-labeling, colocalized with NeuN, and rarely with GFAP, GAD67, or TL. In NT controls and HT rats that did not experience seizures ("HT-no seizures"), approximately 23% of BrdU-labeled cells colocalized with EAAT3, which was significantly different from 14% in HT rats that did experience seizures (HT + FS).


CONCLUSIONS
Early-life seizures decrease the population of newborn cells that survive and mature into EAAT3-positive neurons and do not affect the GABAergic cell population. This may affect hippocampal physiology in young adulthood.
Lemmens
Evi M P
EM
Department of Neurosurgery, University Hospital Maastricht, Maastricht, The Netherlands. evi.lemmens@np.unimaas.nl
Schijns
Olaf E M G
OE
Beuls
Emile A M
EA
Hoogland
Govert
G
D027322:Amino Acid Transport System X-AG / Q000378:metabolism / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D034961:Antigens, Nuclear; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002452:Cell Count; D002455:Cell Division / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology*; D018891:Dentate Gyrus / Q000166:cytology*; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism; D005334:Fever / Q000150:complications*; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein; D005968:Glutamate Decarboxylase; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D017628:Microglia / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D037121:Plant Lectins; D051381:Rats; D017207:Rats, Sprague-Dawley; D003294:Seizures, Febrile / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*
D027322:Amino Acid Transport System X-AG; D034961:Antigens, Nuclear; D050580:Excitatory Amino Acid Transporter 3; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D037121:Plant Lectins; C493398:Slc1a1 protein, rat; C034981:tomato lectin; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D001973:Bromodeoxyuridine