Abstract
To investigate the mechanism of synaptic reorganization in epileptogenesis, we studied dentate granule cell neurogenesis and neuronal loss in the rat kainate model of temporal lobe epilepsy, and their possible association with NMDA receptor activation. In rats, kainate was microinjected into the left amygdala, and limbic status epilepticus was induced. After the kainate injection, bromodeoxyuridine (BrdU) immunohistochemistry and Nissl staining were performed. In addition, MK-801, a selective NMDA receptor antagonist, was administered systemically either once or three times. Kainate-treated rats showed a marked increase in BrdU-positive cells in the bilateral dentate gyrus, while clear neuronal loss was apparent in the CA3 and CA1 regions only on the side ipsilateral to the site of kainate injection. Single pretreatment with MK-801 had no significant effect on kainate-induced enhancement of neurogenesis, whereas treatment with MK-801 three times slightly reduced it. MK-801 also showed significant protective effects against CA1 neuronal damage, but no significant protective effects against CA3 neuronal damage. These results indicate that kainate-induced focal seizure activity enhances adult neurogenesis in the dentate gyrus, which may lead to epileptogenesis independent of hippocampal neuronal damage. The seizure-induced enhancement of neurogenesis may be partly mediated via NMDA receptor activation.
