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

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Abstract
A line of evidence has shown that a link between the common pathological features of β-amyloid peptide (Aβ) deposition and cholinergic degeneration observed in Alzheimer's disease (AD) may exist, however, no experimental evidence has shown that exposure to Aβ 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 Aβ1–40 and Aβ25–35 at nanomolar concentrations significantly decreased the [3H]epibatidine and [125I]α-bungarotoxin binding sites, the protein and mRNA levels of nAChR α3, α7 and β2 subunits in PC12 cells. Aβ1–40 and Aβ25–35 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,diphenyl tetrazolium bromide) reduction. These data suggest that the decreased biosynthesis of nAChRs induced by Aβ may be attributable partially to perturbances of some intracellular signal transduction pathways. The results presented in this study lead to a hypothesis that Aβ can degenerate nAChRs early in the course of AD before the formation of abundant Aβ fibrils.

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