Gender Differences in Febrile Seizure–induced Proliferation and Survival in the Rat Dentate Gyrus


Address correspondence and reprint requests to Dr. E.M.P. Lemmens at Department of Psychiatry and Neuropsychology, Division of Cellular Neuroscience, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. E-mail:


Summary: Purpose: Febrile seizures are fever-associated early-life seizures that are thought play a role in the development of epilepsy. Seizure-induced proliferation of dentate granule cells has been demonstrated in several adult animal models and is thought to be an integral part of epileptogenesis. The aim of the present study was to investigate proliferation and survival of dentate gyrus (DG) cells born after early-life hyperthermia (HT)-induced seizures in male and female rats.

Methods: At postnatal day (PN) 10, male and female rats were exposed to heated air to induce seizures. Littermates were used as normothermia controls. Convulsive behavior was observed by two researchers. From PN11 to PN16, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. The number of BrdU-immunoreactive cells in the DG was counted at PN17 and PN66.

Results: At PN17, male as well as female HT rats had the same amount of BrdU-positive cells compared with controls. At PN66, significantly more BrdU-positive cells were left in HT females (53%) than in controls (44%, percentage of BrdU-positive cells at PN17), whereas no difference was found between HT males and male controls. The net result of proliferation and survival at PN66 was that female HT rats had the same number of BrdU-immunoreactive cells as controls, whereas male HT rats had 25% more BrdU-immunoreactive cells than did controls (p < 0.05).

Conclusions: Early-life seizures cause a sexually dimorphic cytogenic response that results in an increased population of newborn DG cells in young adult males, while leaving that of young adult females unaltered.