Journal
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
Volume 15, Issue 2, Pages 223-233Publisher
OXFORD UNIV PRESS
DOI: 10.1017/S1461145711000162
Keywords
Alzheimer's rat model; APP; nicotinic acetylcholine receptor; psychosocial stress
Funding
- GEAR
- SGP from the University of Houston
- Department of PPS
- Office of the vice-Dean for Research
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In Alzheimer's disease (AD), progressive accumulation of beta-amyloid (A beta) peptides impairs nicotinic acetylcholine receptor (nAChR) function by a mechanism that may involve alpha(7) and alpha(4)beta(2)-nAChR subtypes. Additionally, the beta-site amyloid precursor protein (APP)-cleaving enzyme (BACE), the rate-limiting enzyme in the pathogenic A beta production pathway, is expressed at high levels in hippocampal and cortical regions of AD brains. We measured hippocampal area CA1 protein levels of BACE and alpha(7)- and alpha(4)beta(2)-nAChR subunits using an A beta rat model of AD (14-d osmotic pump i.c.v. infusion of 300 pmol/d A beta peptides) in the presence and absence of chronic stress and/or chronic nicotine treatment. There was a significant increase in the levels of BACE in A beta-infused rats, which were markedly intensified by chronic (4-6 wk) stress, but were normalized in A beta rats chronically treated with nicotine (1 mg/kg b.i.d.). The levels of the three subunits alpha(7), alpha(4) and beta(2) were significantly decreased in A beta rats, but these were also normalized in A beta rats chronically treated with nicotine. Chronic stress did not further aggravate the reduction of nAChRs in A beta-infused rats. The increased BACE levels and decreased nAChR levels, which are established hallmarks of AD, provide additional support for the validity of the A beta i.c.v.-infused rat as a model of AD.
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