Beta-amyloid toxicity and reversal in embryonic rat septal neurons

Alzheimer's disease is characterized mainly by loss of neurons from the septal nucleus. In this study, neurons from the septal nucleus of the embryonic day 16 (E16) rat were grown in culture with a plane of astrocytes from the embryonic rat and in a defined medium in the absence of serum. Neurons were treated with beta-amyloid (A beta: 0.1, 1 and 10 mu M) on day in vitro (DIV) 1 and DIV 4 and fluorescent microscopy was used to measure survival and apoptosis following exposure of the treated cells on DIV 7. Reversal of neurotoxicity was studied using the potentially neuroprotective agents nerve growth factor (NGF, 100 ng/ml), basic fibroblast growth factor (bFGF, 5 ng/ml), insulin-like growth factors (IGF1 and IGF2, 10 ng/ml) and estrogen (10 nM), administered on DIV 4 and DIV 5, that is, subsequent to the A beta (10 mu M)-induced neurotoxicity, A beta caused a significant decrease in survival at 10 mu M, and a significant increase in apoptosis at 0.1 and 10 mu M. IGF1, IGF2 and bFGF all caused a reversal of the A beta-induced neurotoxic effect on survival while NGF and estrogen did not under these experimental conditions. (C) 2007 Elsevier Ireland Ltd. All rights reserved.