Abstracts

Rationale: Neurogenesis in the hippocampal dentate gyrus persists throughout the lifespan of mammals, and the rate of neurogenesis decreases as the animal ages. Although seizures increase neurogenesis in young adult brains, the neurogenic effects of seizures on the aged brain are unknown. Thus, the present study tested the hypothesis that seizures in the aged rat are a sufficient stimulus to increase neurogenesis of dentate granule cells. Methods: We used doublecortin (DCX) immunocytochemistry to study the newly generated neurons in the dentate gyrus. Quantitative morphometrics were used to assess the number of DCX-labeled cells and their basal dendrites in the dentate gyrus from aged rats (24 months of age) at short (5 day) and long (30 day) timepoints after pilocarpine-induced seizures. These data were compared to the data obtained from age-matched controls and from epileptic, young adult rats. The early timepoint was selected because we previously showed that DCX-labeled granule cells display rapid seizure-induced changes. The 30-day time point was analyzed because spontaneous seizures typically occur in the adult rat by this time point after pilocarpine seizures are induced. Results: As shown previously for aged rats from a different strain, the number of DCX-labeled cells in aged rat brains is greatly reduced as compared to that for young adult rat brains. As previously described, DCX-labeled cells had basal dendrites but they appeared to be dysmorphic in both epileptic and control aged brains. When comparing the aged epileptic rats (at both the 5- and 30-day time points) to age-matched controls, there were no significant differences in the number of DCX-labeled cells. Also, there were no significant differences in the number of DCX-labeled cells between the two analyzed time points. The lack of differences could reflect either no response to seizures in the aged brain or a floor effect because the population of DCX-labeled cells in the aged brain is only a small fraction of that in the young adult brain. Conclusions: These data show that the aged brain responds differently to pilocarpine-induced seizures than the young adult brain in that neurogenesis as assessed with DCX-labeling is not increased.