DIFFERENTIAL TRANSCRIPTION AND TRANSLATION OF IMMEDIATE-EARLY GENES IN THE GERBIL HIPPOCAMPUS AFTER TRANSIENT GLOBAL-ISCHEMIA

Excitotoxic activation of glutamate receptors is thought to be a key e vent for the molecular pathogenesis of postischemic delayed neuronal d eath of CA-1 neurons in the gerbil hippocampus. Glutamate receptor sti mulation also causes induction of transcription factors that belong to the class of immediate early genes. We examined the expression of six different immediate early genes in the gerbil hippocampus after trans ient global ischemia. Comparative analysis of c-fos and Krox-24 expres sion was carried out in the same animals at the transcriptional and tr anslational level by in situ hybridization and immunocytochemistry. Po stischemic synthesis of four additional immediate early gene (IEG)-enc oded proteins (FOS-B, c-JUN, JUN-B, and JUN-D) was investigated by imm unocytochemistry at recirculation intervals between 1 and 48 h. After 5 min of ischemia, transcription of c-fos and Krox-24 mRNA was induced in all hippocampal subpopulations with peak expression at 1 h after r ecirculation. In vulnerable CA-1 neurons, increased transcription of c -fos and Krox-24 was not followed by translation into protein. Inducti on of immediate early gene-encoded proteins was restricted to neuronal populations less vulnerable to brief ischemia and identified neurons that are targets of glutamate receptor-mediated neurotoxicity but that are destined to survive. Our data indicate an asynchronous synthesis and persistence of individual IEG-encoded proteins in these neurons. T he staggered induction implies that combinatorial changes of transcrip tion factors allow a differential postischemic regulation of target ge ne expression both spatially and over time.