Chronic ΔFosB 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 upregulation of serum response factor (SRF) in the in vivo pilocarpine model of epilepsy. SRF is established as a regulator of the FosB gene which expresses FosB and ΔFosB components of the AP-1 transcription factor complex. Therefore we investigated whether ΔFosB expression and AP-1 DNA binding were also persistently elevated in pilocarpine-treated rats which chronically displayed spontaneous seizures. Using hippocampal nuclear extracts, ΔFosB expression and AP-1 DNA binding were significantly elevated for up to one year in the epileptic animals. The expression of other fos and jun proteins was not persistently altered in epilepsy. Neuronal upregulation of ΔFosB was correlated with regions of the brain that were involved in seizure generation and propagation. The increase in AP-1 DNA binding was shown to be dependent on NMDA receptor activation during SE. Hippocampal ΔFosB immunostaining was seen predominately in the neuronal nuclei as opposed to other cell types. The data indicate that recurrent seizures which persistently occur in this model were not responsible for the increased ΔFosB expression. Chronic ΔFosB expression in epilepsy may be playing a role in the altered expression of other genes in this model and may be involved in some of the neuronal plasticity changes associated with epileptogenesis.