Nicotine attenuates β-amyloid peptide-induced neurotoxicity, free radical and calcium accumulation in hippocampal neuronal cultures

1 Recent studies indicate that neuronal loss in Alzheimer's disease (AD) is accompanied by the deposition of beta-amyloid protein (Abeta) in senile plaques. Nicotine as a major component of cigarette smoke has been suggested to have a protective effect for neurons against Abeta neurotoxicity. 2 Our present study demonstrates that nicotine protected cultured hippocampal neurons against the Abeta-induced apoptosis. Nicotine effectively inhibits apoptosis in hippocampal cultures caused by Abeta(25-35) or Abeta(1-40) treatment and increase of caspase activity induced by Abeta(25-35) or Abeta(1-40) 3 Measurements of cellular oxidation and intracellular free Ca2+ showed that nicotine suppressed Abeta-induced accumulation of free radical and increase of intracellular free Ca2+. 4 Cholinergic antagonist mecamylamine inhibited nicotine-induced protection against Abeta-induced caspase-3 activation and ROS accumulation. 5 The data show that the protection of nicotine is partly via nicotinic receptors. Our results suggest that nicotine may be beneficial in retarding the neurodegenerative diseases such as AD.