Hippocampal Neurogenesis and Its Phenotypic Differentiation after Kainic Acid-induced Seizures in Mice

ABSTRACT

BACKGROUND: Proliferation and survival of dentate granule cells are influenced by epileptic seizures. Dentate granule cells might play an important role in the pathogenesis of temporal lobe epilepsy. However, most studies have used the rat model. We investigated the neurogenesis of dentate granule cells by the kainic acid (KA)-induced seizure model in ICR mice. METHODS: Seizures were chemically induced by intraperitoneal injections of KA (30 mg/kg) and seizure behavior grades were evaluated. Bromodeoxyuridine (BrdU, 50 mg/kg) was subsequently administered once a day for 6 consecutive days, starting at 24 hours after KA or saline treatment. Mice were sacrificed 7 days after KA administration. The number of BrdU-positive cells in the hippocampus were counted in every seventh section in a series of 30 micrometer coronal sections. We examined the long-term fate of BrdU-labeled cells after KA-induced seizures by double-labeled immunofluorescence with confocal microscopy, 28 days after the last injection of BrdU. RESULTS: After KA administration, every seizure behavior was graded II or more. Quantitative analysis of BrdU labeling revealed a significantly increased proliferation rate of neural precursor cells after seizures. BrdU-positive cells were increased at least 2-fold in KA injection (83.38+/-44.33, n=5) compared to the controls (35.61+/-17.87, n=6). Most of the newborn cells migrated into the granule cell layer from the subgranular zone after KA-induced seizures (n=6, respectively). The majority of these mitotic cells (89%) were differentiated into neurons. CONCLUSIONS: Our results indicated that mitotic activity in the about hippocampus was enhanced after KA-induced seizures in ICR mice, and that the majority of all BrdU-positive cells showed the phenotypic differentiation to neuronal cells.