| Caffeine protects against oxidative stress and Alzheimer's disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet. | |
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MedLine Citation:
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PMID: 20638472 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cholesterol has been linked to the pathogenesis of sporadic Alzheimer's disease (AD) as a risk factor increasing beta-amyloid (Abeta) and oxidative stress levels. Caffeine has antioxidant properties and has been demonstrated to reduce Abeta levels in transgenic mouse models of familial AD. However, the effects of caffeine on cholesterol-induced sporadic AD pathology have not been determined. In this study, we determined the effects of caffeine on Abeta levels, tau phosphorylation, oxidative stress generation, and caffeine-target receptors in rabbits fed a 2% cholesterol-enriched diet, a model system for sporadic AD. Our results showed that the cholesterol-enriched diet increased levels of Abeta, tau phosphorylation, and oxidative stress measured as increased levels of reactive oxygen species and isoprostanes, glutathione depletion, and increased levels of endoplasmic reticulum stress marker proteins. Additionally, the cholesterol-enriched diet reduced the levels of adenosine A(1) receptors (A(1)R) but not ryanodine or adenosine A(2A) receptors. Caffeine, administered at 0.5 and 30mg/day in the drinking water, reduced the cholesterol-induced increase in Abeta, phosphorylated tau, and oxidative stress levels and reversed the cholesterol-induced decrease in A(1)R levels. Our results suggest that even very low doses of caffeine might protect against sporadic AD-like pathology. |
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Authors:
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Jaya R P Prasanthi; Bhanu Dasari; Gurdeep Marwarha; Tyler Larson; Xuesong Chen; Jonathan D Geiger; Othman Ghribi |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-07-16 |
Journal Detail:
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Title: Free radical biology & medicine Volume: 49 ISSN: 1873-4596 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-08-30 Completed Date: 2011-04-11 Revised Date: 2011-10-17 |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: United States |
Other Details:
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Languages: eng Pagination: 1212-20 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alzheimer Disease
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drug therapy*,
etiology,
metabolism Amyloid / biosynthesis*, genetics Animals Caffeine / administration & dosage* Cholesterol, Dietary / adverse effects Cytoprotection Disease Models, Animal Endoplasmic Reticulum / drug effects*, metabolism Hippocampus / drug effects*, metabolism, pathology Humans Male Oxidative Stress / drug effects Rabbits Reactive Oxygen Species / metabolism Receptor, Adenosine A1 / biosynthesis, genetics tau Proteins / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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P20 RR017699-077012/RR/NCRR NIH HHS; P20 RR017699-086122/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amyloid; 0/Cholesterol, Dietary; 0/Reactive Oxygen Species; 0/Receptor, Adenosine A1; 0/tau Proteins; 58-08-2/Caffeine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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