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 follo wing an intrastriatal infusion of quinolinic acid. Fos immunoreactivit y 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 striatum, in regions that subseq uently show little, if any, neurodegeneration. Fos immunoreactivity wa s additionally expressed throughout the ipsilateral cortex. In contras t, Jun immunoreactivity, which remained undetectable for 12 h after th e lesion, reached its maximal intensity 24 h post-lesion, at which tim e 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 str iatum 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 resembl ing those of c-jun mRNA. These results clearly suggest that two distin ct programmes of immediate early gene expression can be induced in viv o. The rapid (2 h) and transient induction of c-fosljun B may well be a response to NMDA receptor activation, whereas the molecular signal f or the late (24 h) and sustained induction of c-jun/fos Bljun D is cur rently a focus for our investigations.