beta-amyloid peptide-induced death of PC 12 cells and cerebellar granule cell neurons is inhibited by long-term lithium treatment

Treatment of rat pheochromocytoma cells (PC 12) cells with beta-amyloid pep tide-(1-42) for 24 h induced a concentration-dependent decrease in cellular redox activity in the dose range of 1 to 20 mu M. These effects were marke dly attenuated by pretreatment with 2 mM LiCl for 7 days, whereas 1-day pre treatment was ineffective. Measurements of live and dead cells by double-st aining with fluorescein diacetate and propidium iodide, respectively reveal ed that protracted lithium pretreatment attenuated PC 12 cell death induced by beta-amyloid-(1-42) and cerebellar granule cell death induced by beta-a myloid-(25-35). Preceding PC 12 cell death, beta-amyloid peptide elicited a slight decrease in protein levels of Bcl-2. Conversely, 7-day pretreatment with lithium resulted in an approximate doubling of Bcl-2 protein levels i n cells treated with or without beta-amyloid peptide-(1-42). Lithium-induce d Bcl-2 upregulation was temporally associated with the cytoprotective effe cts of this drug. Thus, lithium protection against beta-amyloid peptide neu rotoxicity might involve Bcl-2 overexpression, and Lithium treatment for Al zheimer's disease should bit reexamined. (C) 2000 Published by Elsevier Sci ence B.V. All rights reserved.