EFFECT OF BETA-AMYLOID PEPTIDES ON NEURONS IN HIPPOCAMPAL SLICE CULTURES

Several investigators have described the neurotrophic and neurotoxic effects of beta amyloid peptide fragments on dissociated hippocampal neurons in culture. In these prior studies, the peptides were added to dissociated cultures between day 0 and day 4 in vitro, before hippocampal neurons are fully mature. We have analyzed the neurotrophic and neurotoxic effects of beta amyloid fragments beta1-28, beta25-35 and beta1-40 on hippocampal slice cultures, whose physiology and morphology resembles the intact hippocampus. Addition of beta1-28 or beta25-35 to the growth medium did not produce significant changes in dendritic length or number of branches. Nerve growth factor, previously reported to enhance the neurotoxic effects of beta1-40 on dissociated hippocampal neurons in culture, did not significantly enhance the neurotrophic effects of beta1-28. To achieve high local concentrations of peptides and to avoid potential access problems in the cultures, we injected beta1-28, beta25-35, and beta1-40 directly into the cultures. Amyloid-mediated neurotoxicity was not observed for beta1-28 or beta25-35, but beta1-40 appeared to produce neurodegeneration around the site of injection.