Caffeine protects against oxidative stress and Alzheimer's disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet

Jaya R.P. Prasanthi, Bhanu Dasari, Gurdeep Marwarha, Tyler Larson, Xuesong Chen, Jonathan D. Geiger, Othman Ghribi

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Cholesterol has been linked to the pathogenesis of sporadic Alzheimer's disease (AD) as a risk factor increasing β-amyloid (Aβ) and oxidative stress levels. Caffeine has antioxidant properties and has been demonstrated to reduce Aβ 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 Aβ 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 Aβ, 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 A1 receptors (A1R) but not ryanodine or adenosine A2A receptors. Caffeine, administered at 0.5 and 30mg/day in the drinking water, reduced the cholesterol-induced increase in Aβ, phosphorylated tau, and oxidative stress levels and reversed the cholesterol-induced decrease in A1R levels. Our results suggest that even very low doses of caffeine might protect against sporadic AD-like pathology.

Original languageEnglish (US)
Pages (from-to)1212-1220
Number of pages9
JournalFree Radical Biology and Medicine
Volume49
Issue number7
DOIs
StatePublished - Oct 1 2010

Fingerprint

Oxidative stress
Pathology
Nutrition
Caffeine
Hippocampus
Alzheimer Disease
Oxidative Stress
Cholesterol
Diet
Rabbits
Phosphorylation
Adenosine A2A Receptors
Isoprostanes
Adenosine A1 Receptors
Ryanodine
Endoplasmic Reticulum Stress
Heat-Shock Proteins
Amyloid
Drinking Water
Transgenic Mice

Keywords

  • Adenosine receptors
  • Alzheimer's disease
  • Caffeine
  • Cholesterol
  • Endoplasmic reticulum stress
  • Free radicals
  • Oxidative stress
  • Tau
  • β-Amyloid

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Caffeine protects against oxidative stress and Alzheimer's disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet. / Prasanthi, Jaya R.P.; Dasari, Bhanu; Marwarha, Gurdeep; Larson, Tyler; Chen, Xuesong; Geiger, Jonathan D.; Ghribi, Othman.

In: Free Radical Biology and Medicine, Vol. 49, No. 7, 01.10.2010, p. 1212-1220.

Research output: Contribution to journalArticle

@article{56d0994131214950ac3a07503769e685,
title = "Caffeine protects against oxidative stress and Alzheimer's disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet",
abstract = "Cholesterol has been linked to the pathogenesis of sporadic Alzheimer's disease (AD) as a risk factor increasing β-amyloid (Aβ) and oxidative stress levels. Caffeine has antioxidant properties and has been demonstrated to reduce Aβ 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 Aβ 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 Aβ, 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 A1 receptors (A1R) but not ryanodine or adenosine A2A receptors. Caffeine, administered at 0.5 and 30mg/day in the drinking water, reduced the cholesterol-induced increase in Aβ, phosphorylated tau, and oxidative stress levels and reversed the cholesterol-induced decrease in A1R levels. Our results suggest that even very low doses of caffeine might protect against sporadic AD-like pathology.",
keywords = "Adenosine receptors, Alzheimer's disease, Caffeine, Cholesterol, Endoplasmic reticulum stress, Free radicals, Oxidative stress, Tau, β-Amyloid",
author = "Prasanthi, {Jaya R.P.} and Bhanu Dasari and Gurdeep Marwarha and Tyler Larson and Xuesong Chen and Geiger, {Jonathan D.} and Othman Ghribi",
year = "2010",
month = "10",
day = "1",
doi = "10.1016/j.freeradbiomed.2010.07.007",
language = "English (US)",
volume = "49",
pages = "1212--1220",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",
number = "7",

}

TY - JOUR

T1 - Caffeine protects against oxidative stress and Alzheimer's disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet

AU - Prasanthi, Jaya R.P.

AU - Dasari, Bhanu

AU - Marwarha, Gurdeep

AU - Larson, Tyler

AU - Chen, Xuesong

AU - Geiger, Jonathan D.

AU - Ghribi, Othman

PY - 2010/10/1

Y1 - 2010/10/1

N2 - Cholesterol has been linked to the pathogenesis of sporadic Alzheimer's disease (AD) as a risk factor increasing β-amyloid (Aβ) and oxidative stress levels. Caffeine has antioxidant properties and has been demonstrated to reduce Aβ 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 Aβ 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 Aβ, 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 A1 receptors (A1R) but not ryanodine or adenosine A2A receptors. Caffeine, administered at 0.5 and 30mg/day in the drinking water, reduced the cholesterol-induced increase in Aβ, phosphorylated tau, and oxidative stress levels and reversed the cholesterol-induced decrease in A1R levels. Our results suggest that even very low doses of caffeine might protect against sporadic AD-like pathology.

AB - Cholesterol has been linked to the pathogenesis of sporadic Alzheimer's disease (AD) as a risk factor increasing β-amyloid (Aβ) and oxidative stress levels. Caffeine has antioxidant properties and has been demonstrated to reduce Aβ 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 Aβ 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 Aβ, 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 A1 receptors (A1R) but not ryanodine or adenosine A2A receptors. Caffeine, administered at 0.5 and 30mg/day in the drinking water, reduced the cholesterol-induced increase in Aβ, phosphorylated tau, and oxidative stress levels and reversed the cholesterol-induced decrease in A1R levels. Our results suggest that even very low doses of caffeine might protect against sporadic AD-like pathology.

KW - Adenosine receptors

KW - Alzheimer's disease

KW - Caffeine

KW - Cholesterol

KW - Endoplasmic reticulum stress

KW - Free radicals

KW - Oxidative stress

KW - Tau

KW - β-Amyloid

UR - http://www.scopus.com/inward/record.url?scp=77956180469&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956180469&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2010.07.007

DO - 10.1016/j.freeradbiomed.2010.07.007

M3 - Article

C2 - 20638472

AN - SCOPUS:77956180469

VL - 49

SP - 1212

EP - 1220

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 7

ER -