Glucocorticoids exacerbate the deleterious effects of gp120 in hippocampaland cortical explants

Glucocorticoids (GCs), the adrenal steroids secreted during stress, can com promise the ability of hippocampal neurons to survive numerous necrotic ins ults. We have previously observed that GGs worsen the deleterious effects o f gp120, the glycoprotein of the acquired immune deficiency syndrome virus, which can indirectly damage neurons and which is thought to play a role in the neuropathological features of human immunodeficiency Virus infection. Specifically, GCs augment gp120-induced calcium mobilization, ATP depletion , decline in mitochondrial potential, and neurotoxicity in fetal monolayer cultures from a number of brain regions. In the present report, we demonstr ate a similar gp120/GC synergy in adult hippocampal and cortical explants. We generated explants from rats that were either adrenalectomized, adrenall y intact, or intact and treated with corticosterone to produce levels seen in response to major stressors. Metabolic rates in explants were then indir ectly assessed with silicon microphysiometry, and cytosolic calcium concent rations were assessed with fura-2 fluorescent microscopy. We observed that basal levels of GCs tonically augment the disruptive effects of gp120 on me tabolism in the CA1 cell field of the hippocampus and in the cortex. Moreov er, raising GC concentrations into the stress range exacerbated the ability of gp120 to mobilize cytosolic calcium in a number of hippocampal cell fie lds. Finally, we observed that the synthetic GC prednisone had similarly ex acerbating effects on gp120. Thus, GCs can worsen the deleterious effects o f gp120 in a system that is more physiologically relevant than the fetal mo nolayer culture and in a region-specific manner.