Astrocytes contribute to neuronal impairment in βA toxicity increasing apoptosis in rat hippocampal neurons

Astrocytosis is a common feature of amyloid plaques, the hallmark of Alzheimer's disease (AD), along with activated microglia, neurofibrillary tangles, and beta -amyloid (betaA) deposition. However, the relationship between astrocytosis and neurodegeneration remains unclear. To assess whether betaA-stimulated astrocytes can damage neurons and contribute to betaA neurotoxicity, we studied the effects of betaA treatment in astrocytic/neuronal co-cultures, obtained from rat embryonic brain tissue. We found that in neuronal cultures conditioned by betaA-treated astrocytes, but not directly in contact with betaA, the number of apoptotic cells increased, doubling the values of controls. In astrocytes, betaA did not cause astrocytic cell death, nor did produce changes in nitric oxide or prostaglandin E-2 levels. In contrast, S-100 beta expression was remarkably increased. Our data show for the first time that betaA-astrocytic interaction produces a detrimental effect on neurons, which may contribute to neurodegeneration in AD. (C) 2001 Wiley-Liss, Inc.