Astrocytes contribute to neuronal impairment in beta A toxicity increasingapoptosis in rat hippocampal neurons

Astrocytosis is a common feature of amyloid plaques, the hallmark of Alzhei mer's disease (AD), along with activated microglia, neurofibrillary tangles , and beta -amyloid (betaA) deposition. However, the relationship between a strocytosis and neurodegeneration remains unclear. To assess whether betaA- stimulated astrocytes can damage neurons and contribute to betaA neurotoxic ity, we studied the effects of betaA treatment in astrocytic/neuronal co-cu ltures, obtained from rat embryonic brain tissue. We found that in neuronal cultures conditioned by betaA-treated astrocytes, but not directly in cont act with betaA, the number of apoptotic cells increased, doubling the value s of controls. In astrocytes, betaA did not cause astrocytic cell death, no r did produce changes in nitric oxide or prostaglandin E-2 levels. In contr ast, 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.