Caffeine protects against oxidative stress and Alzheimer's disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet.
Caffeine protects against oxidative stress and Alzheimer's disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet.
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DOI：
10.1016/j.freeradbiomed.2010.07.007
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发表时间：
2010-10-15
影响因子：
7.4
通讯作者：
Ghribi, Othman
中科院分区：
文献类型：
--
作者：
Prasanthi, Jaya R. P.;Dasari, Bhanu;Marwarha, Gurdeep;Larson, Tyler;Chen, Xuesong;Geiger, Jonathan D.;Ghribi, Othman
关键词：
胆固醇作为增加β-淀粉样蛋白（Aβ）和氧化应激水平的危险因素与散发性阿尔茨海默病（AD）的发病机制有关。咖啡因具有抗氧化特性，已被证明可降低家族性AD转基因小鼠模型中的Aβ水平。然而，咖啡因对胆固醇诱导的散发性AD病理学的影响尚未确定。在本研究中，我们确定了咖啡因对Aβ水平，tau磷酸化，氧化应激产生和咖啡因靶受体的影响，这些兔喂食2%胆固醇丰富的饮食，这是散发性AD的模型系统。我们的研究结果表明，富含胆固醇的饮食增加了Aβ、tau磷酸化水平以及氧化应激水平，测量为活性氧、异前列腺素、谷胱甘肽耗竭水平增加和内质网（ER）应激标志物蛋白水平增加。此外，富含胆固醇的饮食降低了腺苷A1（A1 R）的水平，但没有ryanodine（RyR）或腺苷A2 A（A2 AR）受体。在饮用水中给予0.5 mg和30 mg/天的咖啡因，可降低胆固醇诱导的Aβ、磷酸化tau蛋白和氧化应激水平升高，并逆转胆固醇诱导的A1 R水平降低。我们的研究结果表明，即使是非常低剂量的咖啡因也可能防止散发性AD样病理。
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 anti-oxidant 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 the present 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 as well as oxidative stress measured as increased levels of reactive oxygen species, isoprostanes, glutathione depletion, and increased levels of endoplasmic reticulum (ER) stress marker proteins. Additionally, the cholesterol-enriched diet reduced levels of adenosine A1 (A1R) but not ryanodine (RyR) or adenosine A2A (A2AR) receptors. Caffeine, administered at 0.5 mg and 30 mg/day in the drinking water, reduced cholesterol-induced increase in Aβ, phosphorylated tau and oxidative stress levels, and reversed cholesterol-induced decrease in A1R levels. Our results suggest that even very low doses of caffeine might protect against sporadic AD-like pathology.
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DOI：
10.3233/jad-2009-1071
发表时间：
2009
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Cao C;Cirrito JR;Lin X;Wang L;Verges DK;Dickson A;Mamcarz M;Zhang C;Mori T;Arendash GW;Holtzman DM;Potter H
通讯作者：
Potter H
影响因子：
30.8
作者：
Harold, Denise;Abraham, Richard;Hollingworth, Paul;Sims, Rebecca;Gerrish, Amy;Hamshere, Marian L.;Pahwa, Jaspreet Singh;Moskvina, Valentina;Dowzell, Kimberley;Williams, Amy;Jones, Nicola;Thomas, Charlene;Stretton, Alexandra;Morgan, Angharad R.;Lovestone, Simon;Powell, John;Proitsi, Petroula;Lupton, Michelle K.;Brayne, Carol;Rubinsztein, David C.;Gill, Michael;Lawlor, Brian;Lynch, Aoibhinn;Morgan, Kevin;Brown, Kristelle S.;Passmore, Peter A.;Craig, David;McGuinness, Bernadette;Todd, Stephen;Holmes, Clive;Mann, David;Smith, A. David;Love, Seth;Kehoe, Patrick G.;Hardy, John;Mead, Simon;Fox, Nick;Rossor, Martin;Collinge, John;Maier, Wolfgang;Jessen, Frank;Schuermann, Britta;van den Bussche, Hendrik;Heuser, Isabella;Kornhuber, Johannes;Wiltfang, Jens;Dichgans, Martin;Froelich, Lutz;Hampel, Harald;Huell, Michael;Rujescu, Dan;Goate, Alison M.;Kauwe, John S. K.;Cruchaga, Carlos;Nowotny, Petra;Morris, John C.;Mayo, Kevin;Sleegers, Kristel;Bettens, Karolien;Engelborghs, Sebastiaan;De Deyn, Peter P.;Van Broeckhoven, Christine;Livingston, Gill;Bass, Nicholas J.;Gurling, Hugh;McQuillin, Andrew;Gwilliam, Rhian;Deloukas, Panagiotis;Al-Chalabi, Ammar;Shaw, Christopher E.;Tsolaki, Magda;Singleton, Andrew B.;Guerreiro, Rita;Muehleisen, Thomas W.;Noethen, Markus M.;Moebus, Susanne;Joeckel, Karl-Heinz;Klopp, Norman;Wichmann, H-Erich;Carrasquillo, Minerva M.;Pankratz, V. Shane;Younkin, Steven G.;Holmans, Peter A.;O'Donovan, Michael;Owen, Michael J.;Williams, Julie
通讯作者：
Williams, Julie
影响因子：
4.3
作者：
Castellani, Rudy J;Zhu, Xiongwei;Smith, Mark A
通讯作者：
Smith, Mark A
影响因子：
3.4
作者：
Devasagayam, TPA;Kamat, JP;Kesavan, PC
通讯作者：
Kesavan, PC
影响因子：
21.3
作者：
Feng, B;Yao, PM;Tabas, I
通讯作者：
Tabas, I