Suppressed expression of nicotinic acetylcholine receptors by nanomolar beta-amyloid peptides in PC12 cells

A line of evidence has shown that a link between the common pathological features of beta -amyloid peptide (A beta) deposition and cholinergic degeneration observed in Alzheimer's disease (AD) may exist, however, no experimental evidence has shown that exposure to A beta can decrease expression of nicotinic acetylcholine receptors (nAChRs), which have been shown to play roles in brain cognitive functions. Here, we report that treatment with A beta (1-40) and A beta (25-35) at nanomolar concentrations significantly decreased the [H-3]epibatidine and [I-125]alpha -bungarotoxin binding sites, the protein and mRNA levels of nAChR alpha3, alpha7 and beta2 subunits in PC12 cells. A beta (1-40) and A beta (25-35) at the concentrations used in the treatment study neither bound to nAChRs nor induced apoptosis, but significantly inhibited the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5,diphenylthiazol-2-yl)-2,5,diphenyl tetrazolium bromide) reduction. These data suggest that the decreased biosynthesis of nAChRs induced by A beta may be attributable partially to perturbances of some intracellular signal transduction pathways. The results presented in this study lead to a hypothesis that A beta can degenerate nAChRs early in the course of AD before the formation of abundant A beta fibrils.