title: Nicotine modifies in vivo and in vitro rat hippocampal amyloid precursor protein processing in young but not old rats.
abstract: Previous studies have shown that administration of nicotine modifies the expression and secretion of amyloid precursor protein (APP) in various cell lines. The present study investigated the extent to which chronic subcutaneous nicotine administration influences APP levels and processing in cerebral cortex, striatum and hippocampus of young and old rat brains. The results showed that constant nicotine infusion (0.25 or 4.00mg/kg/day) increased the levels of particulate APP (APPp) but not secreted APP (APPs) in the hippocampus of young rats in vivo. This response to nicotine was not observed in the striatum or cerebral cortex of young rats or in any of the brain regions examined in old animals. Subsequent in vitro analysis demonstrated that nicotine enhanced the release of APPs from hippocampal slice preparations and that this increase was attenuated by mecamylamine, a non-selective nicotinic acetylcholine receptor (nAChR) antagonist. The in vitro effect of nicotine on APPs was age-related, being only detected from hippocampal slices derived from the young but not the older animals. These results suggest that nicotine modulates APP expression and secretion in the hippocampus and that the responses observed to the drug are age-dependent being only detected in younger rats.
authors.affiliation: Division of Neuroscience, Medical Research Institute, University of Dundee, Ninewells Hospital & Medical School, Dundee DD1 9SY, UK. charles.scerri@um.edu.mt
authors.forename: Charles
authors.initials: C
authors.lastname: Scerri
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Stewart
authors.forename: David J K
authors.initials: DJ
authors.lastname: Balfour
authors.forename: Kieran C
authors.initials: KC
authors.lastname: Breen
mesh_terms: D000367:Age Factors; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016564:Amyloid beta-Protein Precursor; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D008464:Mecamylamine; D009538:Nicotine