Low concentrations of estradiol reduce β-amyloid (25-35)-induced toxicity, lipid peroxidation and glucose utilization in human SK-N-SH neuroblastoma cells

The present studies were undertaken to determine the role of physiologically relevant concentrations of estrogens on amyloid-induced changes in cell viability, metabolic demands, and lipid peroxidation in response to the toxic fragment of beta-amyloid (beta AP 25-35). To this end, SK-N-SH human neuroblastoma cells were exposed to beta AP 25-35 or beta AP 25-35 plus 17 beta-estradiol, and cell viability, media glucose use and lactate production were measured at time points ranging from 3 to 15 h for examination of acute effects, or at 48 and 72 h time points for chronic effects. Addition of beta AP 25-35 to SK-N-SH cells decreased the number of viable cells from 5% at 3 h to 35% at 15 h when compared to vehicle controls. Chronic treatment for 48 and 72 h caused decreases in viable cell number of 70% and 65%, respectively. Paradoxically, both glucose utilization and lactate production were found to be increased for the beta AP-treated cells. Concomitant estrogen treatment was found to be neuroprotective, as the severity of the insult on cell viability was decreased by 40% at 15 h and up to 71% at 72 h. Likewise, the addition of 17 beta-estradiol decreased both the glucose use and lactate production of the cells. Chronic treatment with beta AP caused increases in lipid peroxidation over vehicle treated controls of 82% and 78% at 48 and 72 h, respectively, while decreases in peroxidation of 48% were seen with simultaneous estrogen treatment. These results indicate that the neuroprotective effects of estrogens against beta AP-induced toxicity are due in part to their capability to decrease lipid peroxidation and may additionally be attributable to decreasing the metabolic load of the cell. (C) 1997 Elsevier Science B.V.