Immediate early gene expression in the rat forebrain following striatal infusion of quinolinic acid.

Expression in the rat forebrain of immediate early genes belonging to the fos and jun families was investigated at various time points following an intrastriatal infusion of quinolinic acid. Fos immunoreactivity was rapidly and transiently induced, exhibiting maximal intensity 2 h post-lesion, and was principally located in neuronal nuclei situated around the periphery of the lesioned straitum, in regions that subsequently show little, if any, neurodegeneration. Fos immunoreactivity was additionally expressed throughout the ipsilateral cortex. In contrast, Jun immunoreactivity, which remained undetectable for 12 h after the lesion, reached its maximal intensity 24 h post-lesion, at which time it was most densely distributed in neuronal nuclei found within the central lesioned areas of the striatum. In situ hybridization analysis using radiolabelled oligonucleotide probes confirmed this spatial and temporal separation between c-fos and c-jun expression within the striatum and extended it further, showing that, whilst jun mRNA displayed very similar expression characteristics to those of c-fos mRNA, both fos B mRNA and jun D mRNA exhibited induction patterns closely resembling those of c-jun mRNA. These results clearly suggest that two distinct programmes of immediate early gene expression can be induced in vivo. The rapid (2 h) and transient induction of c-fos/jun B may well be a response to NMDA receptor activation, whereas the molecular signal for the late (24 h) and sustained induction of c-jun/fos B/jun D is currently a focus for our investigations.