Responses of Cultured Astrocytes, C6 Glioma and 1321NI Astrocytoma Cells to Amyloid beta-Peptide Fragments.

Abstract

The effect of amyloid beta-peptide (betaAP), which can have both neurotrophic or neurotoxic effects on neurons and has been implicated in the pathogenesis of Alzheimer's disease (AD), was studied on astrocytes using primary cultures and astrocyte cell lines (rat C6 glioma, human 1321NI astrocytoma cells). The cultures were exposed to 0.0005-50 mug/ml) betaAP fragments 1-40, 25-35, 31-35, or 40-41 (control) for 24 hr. Some of the fragments were maintained at 37 degrees C for 48 hr to induce aggregation and some of the cell cultures were pretreated with the differentiating agent dBcAMP before the experiments. The astrocyte responses were evaluated for lysosome activity (neutral red assay) and levels of structural proteins, glial fibrillary acidic protein, vimentin, and S-100, which are altered in the dystrophic plaques with associated astrogliosis in AD. The cells frequently responded with biphasic responses, with initial (low-dose) activation-type responses (i.e., increases of indicator compared to controls), before reductions with altered morphology (increased branching of cells) at higher concentrations. However, cell death (with EC(50) values) was not observed, even at the maximum concentrations of betaAP fragments. The findings suggest that the astrocytes have a relatively high resistance against the betaAP toxicity.