Sequential changes in AMPA and NMDA protein levels during Fe3+-induced epileptogenesis

Seizure susceptibility is related to enhanced glutamatergic excitatory syna ptic transmission with alterations in the expressions of ionotropic glutama te receptors. We wondered if levels of AMPA and NMDA receptor subunits chan ged following epileptogenesis induced by amygdalar FeCl3 injection. We used Western blots to measure levels of subunits in the ipsilateral and contral ateral hippocampus at various times after FeCl3 injection into the amygdalo id body. With acute seizures, at +5 days after the injection, levels of Glu R1, NMDAR1, and NMDAR2 were markedly increased in both hippocampi, with qua ntities at least 2-4 times baseline. By +15 and +30 days after injection, w hen chronic spontaneous seizures were occurring, the levels of GluR2 were i ncreased, while GluR1 and NMDAR1&2A/B were decreased. Increased NMDAR1&2A/B levels at +5 days are consistent with the occurrence of upregulation of NM DA receptor production in the early stages of epileptogenesis. Since GluR2 suppresses glutamate receptor-mediated Ca2+-influx, increased expression of GluR2 with development of chronic, recurrent seizures may be a compensator y effect during epileptogenesis from neural responses to propagated seizure s. (C) 2001 Elsevier Science BY All rights reserved.