Expression of c- jun, junB, c- fos, fra-1 and fra-2 mRNA in the rat brain following seizure activity and axotomy

Abstract

The present study has investigated the congruence of mRNA induction and protein expression of inducible transcription factors (ITFs). The patterns of c- jun, junB, c- fos, fra-1 and fra-2 mRNAs were studied by radioactive and non-radioactive in situ hybridization in the adult rat brain following kainate-induced seizure activity and axotomy. In the same animals, the expression of c-Jun, JunB and c-Fos proteins was compared with the respective mRNA signals. Using radioactive labeled probes all investigated mRNAs showed an onset within 1 h after systemic kainate application and the maximal levels were generally reached after 3 h. Each mRNA displayed a specific temporo-spatial expression pattern. Whereas fra-1 and fra-2 were restricted to the hippocampus, c- jun, junB and c- fos were additionally induced in the cortex, amygdala and thalamus. The areas with maximal labeling were the dentate gyrus and the hippocampal CA1 and CA3 subfields. The expression patterns between c- jun, junB and c- fos mRNA were virtually congruent with the respective protein. Labeling of the junB and fra-2 probes with digoxigenin yielded similar results. Twenty-four hours, 3 and 10 days following transection of the medial forebrain bundle and the mamillo-thalamic tract, high levels of c- jun mRNA (either digoxigenin or radioactive labeled probes) and protein were seen in the axotomized neurons of the substantia nigra pars compacta and mamillary body whereas the other mRNAs studied and the JunB or c-Fos proteins could not be detected. These findings demonstrate that mRNAs encoding for ITFs are translated into the respective proteins following excitotoxic seizures and axotomy, and that the antisera used for immunocytochemistry yield specific expression patterns of homologous proteins.