Cyclic AMP responsive element- and activator protein 1 DNA-binding activities in epilepsy model mice

Convulsive seizures caused by many different stimuli have been shown to ind uce activator protein-1 (AP-1) transcription factors in the brain, particul arly in the hippocampus. Previous results from our laboratory demonstrated that thalamic and cerebral cortical AP-1 DNA- and cyclic AMP responsive ele ment (CRE)- binding activities in the absence seizure model mice were signi ficantly higher than those in nonepileptic control mice. In order to charac terize further a correlation between convulsive seizures and inducible tran scription factors, we investigated convulsive seizure-dependent increases i n AP-1 DNA- and CRE-binding activities in various brain regions of the mice . Administration of pentylentetrazole and kainic acid provoked clonic and l imbic type seizures, respectively, and increased AP-1 DNA- and CRE-binding activities in the cerebral cortex and hippocampus but not in other regions. Maximal electric shock (MES) induced tonic convulsions and increased hippo campal and cerebral cortical AP-1 DNA- and CRE- binding activities. Sodium phenobarbital (50 mg/kg, i.p.), an anticonvulsant, suppressed both convulsi ons and increases in these DNA-binding activities induced by MES. In contra st, ethosuximide, an antiabsence drug, did not affect MES-induced convulsio ns or increases in these DNA-binding activities. These data suggest that co nvulsive seizures increase not only AP-1 DNA-binding but also CRE-binding a ctivities in the cerebral cortex and hippocampus. These data combined with our previous results also suggest that regional differences in increases in CRE- and AP-1 DNA-binding activities between convulsive seizures and absen ce seizures are attributable to differences in the regions and pathways whi ch are responsible for the genesis and spreading seizure activities in the central nervous system.