Induction of FOS and JUN proteins during focal epilepsy: congruences with and differences to [14C]deoxyglucose metabolism.

Abstract

fos and jun belong to multigene families coding for transcription factors. These cellular immediate-early genes (IEGs) are thought to be involved in coupling neuronal excitation to changes of target gene expression. Immunocytochemistry with specific antisera was used to assess regional levels of five IEG-encoded proteins (c-FOS, FOS B, c-JUN, JUN B and JUN D) in a rat model of penicillin-induced focal epilepsy. To assess whether brain regions with post-ictal de novo transcription factor synthesis correspond to those areas with increased glucose metabolism, IEG expression patterns were compared with [14C]deoxyglucose autoradiography performed in a subset of animals. The results demonstrated marked induction of c-FOS, FOS B, c-JUN and JUN B but not JUN D in the cortical epileptic focus. Thereby, individual IEG-encoded proteins exhibited differential temporal and spatial expression patterns. Within the epileptic focus, IEG expression correlated with increased glucose metabolism. In contrast, IEG induction was not observed in brain areas distant from the epileptic focus that also demonstrated increased glucose metabolism, such as homotopic contralateral motor cortex and ipsilateral thalamic nuclei. These findings indicate that in focal epilepsy changes of the genetic programme are restricted to neurons of the epileptic focus. In contrast, the increased [14C]deoxyglucose metabolism in contralateral motor cortex and ipsilateral thalamus seems to indicate functional changes.