Differential expression of the immediate early genes c-fos, c-jun, junB, and NGFI-B in the rat brain following transient forebrain ischemia.

Abstract

The temporospatial expression pattern of four immediate early genes (IEGs) (c-fos, c-jun, junB, NGFI-B) following 30 min of global ischemia was investigated in rat brains by in situ hybridization and immunohistochemistry (c-fos). All examined IEG mRNAs, as well as Fos-like immunoreactivity, increased transiently in vulnerable and resistant brain regions following ischemia, but the induction profiles were distinct. Ischemia caused a post-ischemic early-onset, transient c-fos induction in wide-spread regions, as well as a late-onset induction restricted to vulnerable regions. Late-onset c-fos induction was observed in the CA1 region and the ventral thalamus but not in the striatum or neocortex, where neurons degenerate at a quicker pace. After recirculation, c-jun mRNA appeared to be initially coinduced with c-fos mRNA, but c-jun mRNA levels remained elevated or increased in various regions, including all vulnerable regions, when c-fos mRNA had already declined to near basal levels. Compared to c-fos and c-jun, junB induction was less pronounced and confined largely to the dentate gyrus. NGFI-B mRNA increased moderately and only in brain regions exhibiting the most dramatic c-fos increases and with similar kinetics. The differential activation of the investigated IEGs suggests that rather complex long-term adaptive processes may be initiated at the genomic level after global ischemia. The present findings provide further evidence that the activation of IEGs forms part of the brain's metabolic response to ischemia, but no simple correlation appears to exist between the induction of the investigated IEGs and the phenomenon of selective vulnerability.