TRANSIENT EXPRESSION OF THE MITOGEN-ACTIVATED PROTEIN-KINASE PHOSPHATASE MKP-1 (3CH134 ERP1) IN THE RAT-BRAIN AFTER LIMBIC EPILEPSY/

The immediate early gene-encoded enzyme, MAP kinase phosphatase 1 (MKP -1), is thought to be a key element in controlling cellular signalling pathways activated by MAP kinases. Since MAP kinases have been demons trated to participate in neuronal stimulus-transcription coupling foll owing seizure activity, the present study investigated the induction o f MKP-1 in the rat brain after limbic epilepsy. MKP-1 expression was s tudied with a polyclonal antiserum by Western blots, immunocytochemist ry and immuno-electron microscopy at different time periods between 1 and 24 h after kainic acid-induced limbic seizures. MKP-1 induction wa s identified in dentate granule cells of the hippocampus but not in py ramidal neurons, furthermore in neurons of the outer layers of the neo cortex, as well as in neurons of the lateral nucleus of the bed of the stria terminalis. Immune-electron microscopy demonstrated that MKP-1 was localized in the neuronal nucleus, where the substrate of MKP-1, a ctivated MAP kinases, are also found, In view of the restricted areas of MKP-1 expression and the widespread areas of altered MAP kinases ac tivity it can be concluded that in the majority of CNS populations oth er mechanisms than MKP-1 induction are responsible for the shut-off of MAP kinases following seizure activity, MKP-1 may contribute in the s pecific subpopulations where it is induced to the post-translational c ontrol of inducible transcription factors of the fos, jun and myc fami ly.