Nicotine modulates the neurotoxic effect of beta-amyloid protein(25-35)) in hippocampal cultures.

Two major features of Alzheimer's disease (AD) are beta-amyloid protein (beta AP) deposition and a severe cholinergic deficit. An association between the two is suggested by the negative correlation found between cigarette smoking and AD. We sought to investigate this further by examining the effects of acute and chronic nicotine exposure on beta AP-induced neuronal loss in rat hippocampal cultures. Nicotine was found to attenuate the neurotoxicity of higher concentrations of beta AP(25-35), an effect which was enhanced by longer nicotine pretreatment and significantly inhibited by the nicotine receptor antagonist mecamylamine. Our results suggest that nicotine partially protects against the neurotoxic actions of beta AP(25-35) via a receptor-mediated pathway.

Neurotoxicity of beta-amyloid protein: cytochemical changes and apoptotic cell death investigated in organotypic cultures.

1. This study is an attempt to examine in vitro the cytochemical changes in hippocampal neurones induced by beta-amyloid protein (beta-AP). 2. The mechanism of cell death, and the vulnerability of different regions of the hippocampus to b-AP toxicity, has also been explored using TUNEL staining to locate fragmented DNA in both dissociated and organotypic cultures. 3. Apoptotic cell profiles and the detection by immunocytochemistry of ubiquitin and tau protein confirmed the acute neurodegenerative effects of b-AP, and organotypic cultures revealed the dentate gyrus to be especially vulnerable. 4. A scrambled sequence of b-AP, a peptide with similar hydrophobic groups to b-AP, and islet pancreatic amyloidogenic peptide also showed neurodegenerative effects, although less severely than b-AP. 5. It is concluded that organotypic cultures provide a valuable in vitro model with which to observe and characterize the neurotoxic effects of b-AP. These effects, however, may be non-specific and related more to the general amyloidogenicity of the b-AP molecule.