AP-1 and CRE DNA binding activities in rat brain following pentylenetetrazole induced seizures

Pentylenetetrazole (PTZ) evoked seizures, known to be dependent on stimulation of excitatory amino acids (EAA) receptors, serve as a useful model to study genomic responses to increased brain activity. It is believed that these responses form the basis for long term modifications in neuronal functions. Formation of the AP-1 transcription factor genes and proteins in hippocampal cells is the best known example of a genomic response to PTZ seizures and to an activation of the EAA receptors. In the studies reported herein electrophoretic mobility shift assay (EMSA) was employed to investigate levels of AP-1 DNA binding activity in various regions of the rat brain following PTZ seizures and these levels were compared to the cyclic AMP responsive element (CRE) DNA binding activity. A dramatic increase of the AP-1 DNA binding activity was observed in the hippocampus and in sensory and limbic cortices, and to much lesser extent in the cerebellum. The EMSA supershift method provided an evidence that Jun B and c-Fos and probably Fos B are major components of AP-1 at 2 h after the seizures. In none of the structure investigated, clear modulation of CRE DNA binding activity was noted. These data are discussed in the context of CRE and AP-1 DNA binding crossreactivity.