Adrenalectomy regulates apoptotic-associated genes in rat hippocampus

Morphological studies of granular neurons of the hippocampus have shown tha t adrenalectomy (ADX) induces the cell death of granular neurons, an effect prevented by corticosterone replacement. We addressed the hypothesis that corticosterone regulates the expression of the apoptotic bcl-2 gene family. Five days after adrenalectomy, we observed morphological changes related t o hippocampal granule cell apoptosis that was accompanied by terminal dUTP nick and labeling (TUNEL) labeling in nuclei located in the hilus region. C orticosterone replacement prevented the cell death induced by ADX. Using RT -PCR we found a reduction in mRNA levels of the antiapoptotic gene bcl-2 in whole hippocampus, an effect which was prevented by corticosterone adminis tration to ADX rats. However, Bcl-2 protein levels were not altered by this treatment. We did not observe modifications in the level of bcl-X-L mRNA h owever, we did find a 40% reduction in Bcl-X-L protein levels, an effect no t reversed by corticosterone. In contrast, we found a reduction in the mRNA of the antiapoptotic gene bax and Bax levels after ADX; both effects were prevented by corticosterone. The reduction in proapoptotic bax and in antia poptotic bcl-2 mRNA levels in the whole hippocampus, suggests that local va riations in these molecules could account for both neuronal viability of th e CA1-CA3 and granular cell death detected by morphological means and obser ved after ADX.