Hippocampal Neurogenesis and Phenotypic Differentiation after Pilocarpine-Induced Seizures in Young Mice

Park, Jiwon; Ryu, Na Yung; Kim, Dong Wook

Abstract

PURPOSE
Proliferation, differentiation, and survival of hippocampal dentate granule cells have been reported to be influenced by epileptic seizures in rodent epilepsy models. However, most studies have been done in adult rat models. This study was designed to investigate hippocampal dentate granule cell neurogenesis after pilocarpine-induced seizures in young mice.
METHODS
Fifteen male ICR mice at postnatal day 21 were divided into pilocarpine-treated (n=7) and control (n=8) groups. Seizures were chemically induced by intraperitoneal injection of pilocarpine (300 mg/kg). Bromodeoxyuridine (BrdU, 50 mg/kg) was subsequently administered once a day for 6 consecutive days, starting at 24 hours after pilocarpine or saline treatment. We then examined BrdU-positive cells in the hippocampal dentate gyrus by immunohistochemistry and by double-labeled immunofluorescence with confocal microscopy.
RESULTS
After pilocarpine administration, every seizure behavior was grade 3 or more. Quantitative analysis revealed that BrdU-positive cells were significantly increased in the pilocarpine-treated group compared to control (230.5+/-59.5 vs. 148.6+/-40.0, P<0.001). The majority of these mitotic cells were differentiated into neurons.
CONCLUSION
Our results indicated that mitotic activity in the hippocampal dentate gyrus was enhanced after pilocarpine-induced seizures in young mice, and the majority of BrdU-positive cells showed the phenotypic differentiation to neuronal cells.