Adrenalectomy Regulates Apoptotic-Associated Genes in Rat Hippocampus

Abstract

Morphological studies of granular neurons of the hippocampus have shown that 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 to hippocampal granule cell apoptosis that was accompanied by terminal dUTP nick and labeling (TUNEL) labeling in nuclei located in the hilus region. Corticosterone 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 administration 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 however, we did find a 40% reduction in Bcl-X(L) protein levels, an effect not 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 antiapoptotic bcl-2 mRNA levels in the whole hippocampus, suggests that local variations in these molecules could account for both neuronal viability of the CA1-CA3 and granular cell death detected by morphological means and observed after ADX.

Desipramine prevents stress-induced changes in depressive-like behavior and hippocampal markers of neuroprotection

“…Whole hippocampal homogenates were prepared as described earlier (Greiner et al, 2001;Andres et al, 2006). Seventy-five micrograms of protein from each homogenate were resolved by electrophoresis on 12% SDS-polyacrylamide gels, and electrotransferred onto 0.22-mm nitrocellulose membranes.…”

Neuroprotection provided by dietary restriction in rats is further enhanced by reducing glucocortocoids

“…Slightly elevated levels of CORT in plasma (200–270 nM range) in the rat have been reported to attenuate N-methyl-D-aspartate (NMDA) and amyloid-β toxicity, while chronic elevation (310–650 nM range) potentiated the neurotoxic effects in the nucleus basalis magnocellularis (Abraham et al, 2006). Moreover, absence of CORT for 3 days due to adrenalectomy (ADX) can result in apoptosis of granule cells of the dentate gyrus (DG) in adult rats (Greiner et al, 2001). Reduction of CORT in ad libitum fed rats by ADX produced hypophagia and satiety (Torres et al, 2008) and decreased locomotor activity (Duclos et al, 2009).…”

Dietary restriction and brain health

“…Moreover, it is also found that the replacement of corticosterone can prevent the reduction of bcl-2 gene expression after ADX [86] . Secondly, it has been found that corticosterone can facilitate and enhance memory consolidation [87] .…”

“…Firstly, the physiological level of corticosterone is critical for neuronal survival. Adrenalectomy (ADX), which means removal of the major organism for synthesizing corticosterone, can induce cell death of granular neurons in the hippocampus, while replacement of corticosterone could then block this neuronal death [86] .…”