Chronic Delta FosB expression and increased AP-1 transcription factor binding are associated with the long term plasticity changes in epilepsy

NMDA receptor activation during status epilepticus (SE) has previously been shown to be required for epileptogenesis as well as the persistent upregul ation of serum response factor (SRF) in the in vivo pilocarpine model of ep ilepsy. SRF is established as a regulator of the FosB gene which expresses FosB and Delta FosB components of the AP-I transcription factor complex. Th erefore we investigated whether Delta FosB expression and AP-1 DNA binding were also persistently elevated in pilocarpine-treated rats which chronical ly displayed spontaneous seizures. Using hippocampal nuclear extracts, Delt a FosB expression and AP-1 DNA binding were significantly elevated for up t o one year in the epileptic animals. The expression of other fos and jun pr oteins was not persistently altered in epilepsy. Neuronal upregulation of D elta FosB was correlated with regions of the brain that were involved in se izure generation and propagation. The increase in AP-I DNA binding was show n to be dependent on NMDA receptor activation during SE. Hippocampal Delta FosB immunostaining was seen predominately in the neuronal nuclei as oppose d to other cell types. The data indicate that recurrent seizures which pers istently occur in this model were not responsible for the increased Delta F osB expression. Chronic Delta FosB expression in epilepsy may be playing a role in the altered expression of other genes in this model and may be invo lved in some of the neuronal plasticity changes associated with epileptogen esis. (C) 2000 Elsevier Science B.V. All rights reserved.