Sequential changes in AMPA and NMDA protein levels during Fe(3+)-induced epileptogenesis

Seizure susceptibility is related to enhanced glutamatergic excitatory synaptic transmission with alterations in the expressions of ionotropic glutamate receptors. We wondered if levels of AMPA and NMDA receptor subunits changed following epileptogenesis induced by amygdalar FeCl(3) injection. We used Western blots to measure levels of subunits in the ipsilateral and contralateral hippocampus at various times after FeCl(3) injection into the amygdaloid body. With acute seizures, at +5 days after the injection, levels of GluR1, NMDAR1, and NMDAR2 were markedly increased in both hippocampi, with quantities at least 2-4 times baseline. By +15 and +30 days after injection, when chronic spontaneous seizures were occurring, the levels of GluR2 were increased, while GluR1 and NMDAR1&2A/B were decreased. Increased NMDAR1&2A/B levels at +5 days are consistent with the occurrence of upregulation of NMDA receptor production in the early stages of epileptogenesis. Since GluR2 suppresses glutamate receptor-mediated Ca(2+)-influx, increased expression of GluR2 with development of chronic, recurrent seizures may be a compensatory effect during epileptogenesis from neural responses to propagated seizures.