HIGH INDUCTION THRESHOLD FOR TRANSCRIPTION FACTOR KROX-20 IN THE RAT-BRAIN - PARTIAL COEXPRESSION WITH HEAT-SHOCK PROTEIN-70 FOLLOWING LIMBIC SEIZURES

The transcription factor KROX-20, unlike many other immediate early ge nes, is not expressed in the rat hippocampus after bicuculline induced generalized seizures. Since limbic seizures are a more injurious stim ulus, the KROX-20 expression profile was investigated in adult rats su bjected to kainic acid induced limbic epilepsy at postictal intervals up to 48 h. Immunocytochemistry was performed using a specific polyclo nal antiserum. In the hippocampus a sequential induction was observed with peak levels attained in dentate gyrus at 3 h, in CA1 at 8 h and i n CA3 between 8 and 24 h, respectively. In contrast, no KROX-20 induct ion was found in hilus neurons. Prominent neuronal KROX-20 induction w as also detected in other areas of the limbic system, in particular in amygdala and piriform cortex, as well as non-limbic regions such as n eocortex and striatum. As is the case with KROX-20, heat shock protein (HSP) 70, a reliable marker for reversible neuronal injury, has a hig h induction threshold. Though not inducible in the hippocampus by gene ralized seizures, it is expressed after limbic epilepsy. Therefore, co -expression of KROX-20 and HSP70 was studied by a double labeling tech nique using a monoclonal antibody directed against the inducible form of HSP70. Neuronal subpopulations with perfect co-expression such as h ippocampal CA1 neurons contrasted with others demonstrating partial co -induction (cortical neurons) or lack of co-expression (hilus cells), indicating that different stimuli trigger the activation of these two inducible genes.