Document Detail


Caffeine protects against oxidative stress and Alzheimer's disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet.
MedLine Citation:
PMID:  20638472     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jaya R P Prasanthi; Bhanu Dasari; Gurdeep Marwarha; Tyler Larson; Xuesong Chen; Jonathan D Geiger; Othman Ghribi
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-07-16
Journal Detail:
Title:  Free radical biology & medicine     Volume:  49     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-08-30     Completed Date:  2011-04-11     Revised Date:  2011-10-17    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1212-20     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, USA.
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MeSH Terms
Descriptor/Qualifier:
Alzheimer Disease / 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:
P20 RR017699-077012/RR/NCRR NIH HHS; P20 RR017699-086122/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid; 0/Cholesterol, Dietary; 0/Reactive Oxygen Species; 0/Receptor, Adenosine A1; 0/tau Proteins; 58-08-2/Caffeine

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