Dentate Granule Cell Neurogenesis Is Increased by Seizures and Contributes to Aberrant Network Reorganization in the Adult Rat Hippocampus

摘要: The dentate granule cell layer of the rodent hippocampal formation has distinctive property ongoing neurogenesis that continues throughout adult life. In both human temporal lobe epilepsy and models limbic epilepsy, this same neuronal population undergoes extensive remodeling, including reorganization mossy fibers, dispersion layer, appearance cells in ectopic locations within gyrus. mechanistic basis these abnormalities, as well their potential relationship to neurogenesis, is unknown. We used a systemic chemoconvulsant model bromodeoxyuridine (BrdU) labeling investigate effects prolonged seizures on rats, examine contribution newly differentiated network changes seen model. Pilocarpine-induced status epilepticus caused dramatic increase proliferation subgranular proliferative zone (SGZ), an area known contain precursor cells. Colocalization BrdU-immunolabeled with neuron-specific markers turned after division, 64 kDa, class III β-tubulin, or microtubule-associated protein-2 showed vast majority mitotically active into neurons layer. Newly generated also appeared hilus inner molecular Furthermore, developing projected axons aberrantly CA3 pyramidal region Induction seizure activity by perforant path stimulation resulted SGZ mitotic similar pilocarpine administration. These observations indicate discharges stimulate plasticity associated epileptogenesis may arise from aberrant connections formed born