Nicotinic receptor stimulation protects neurons against β‐amyloid toxicity

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Abstract
β-Amyloid (Aβ), a major constituent of senile plaques in Alzheimer's disease (AD), is thought to contribute to the neurodegeneration. We examined the effects of nicotinic receptor agonists on Aβ cytotoxicity in cultured rat cortical neurons. The number of viable neurons decreased significantly when cultures were exposed to synthetic Aβ peptides (25–35). Concomitant administration of nicotine with Aβ markedly reduced the number of dead cells. This nicotine-induced neuroprotection was dependent on the concentration. When hexamethonium or mecamylamine, nicotinic antagonist, was added, neuroprotective effect of nicotine was blocked, which indicates that effect of nicotine was mediated by nicotinic receptors. In addition, a selective α7-receptor antagonist, α-bungarotoxin (α-BTX), blocked the neuroprotective effect of nicotine. Furthermore, incubation with 3–(2,4)-dimethoxybenzylidene anabaseine (DMXB), a selective α7–receptor agonist, protected against Aβ-induced neuronal death. These results suggest that α7–receptor activation plays an important role in neuroprotection against Aβ cytotoxicity. This study suggests that nicotinic receptor stimulation, especially α-receptor activation, may be able to protect neurons from degeneration induced by Aβ and may have effects that counter the progress of AD.