| Elevation of BACE in an Aβ rat model of Alzheimer's disease: exacerbation by chronic stress and prevention by nicotine. | |
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MedLine Citation:
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PMID: 21356140 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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In Alzheimer's disease (AD), progressive accumulation of β-amyloid (Aβ) peptides impairs nicotinic acetylcholine receptor (nAChR) function by a mechanism that may involve α7 and α4β2-nAChR subtypes. Additionally, the beta-site amyloid precursor protein (APP)-cleaving enzyme (BACE), the rate-limiting enzyme in the pathogenic Aβ 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 α7- and α4β2-nAChR subunits using an Aβ rat model of AD (14-d osmotic pump i.c.v. infusion of 300 pmol/d Aβ 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 Aβ-infused rats, which were markedly intensified by chronic (4-6 wk) stress, but were normalized in Aβ rats chronically treated with nicotine (1 mg/kg b.i.d.). The levels of the three subunits α7, α4 and β2 were significantly decreased in Aβ rats, but these were also normalized in Aβ rats chronically treated with nicotine. Chronic stress did not further aggravate the reduction of nAChRs in Aβ-infused rats. The increased BACE levels and decreased nAChR levels, which are established hallmarks of AD, provide additional support for the validity of the Aβ i.c.v.-infused rat as a model of AD. |
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Authors:
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Karim A Alkadhi; Karem H Alzoubi; Marisa Srivareerat; Trinh T Tran |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-2-28 |
Journal Detail:
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Title: The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) Volume: - ISSN: 1469-5111 ISO Abbreviation: - Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-3-1 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9815893 Medline TA: Int J Neuropsychopharmacol Country: - |
Other Details:
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Languages: ENG Pagination: 1-11 Citation Subset: - |
Affiliation:
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Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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