Caffeine blocks disruption of blood brain barrier in a rabbit model of Alzheimer's disease.
Caffeine blocks disruption of blood brain barrier in a rabbit model of Alzheimer's disease.
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DOI：
10.1186/1742-2094-5-12
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发表时间：
2008-04-03
影响因子：
9.3
通讯作者：
Geiger, Jonathan D
中科院分区：
文献类型：
--
作者：
Chen, Xuesong;Gawryluk, Jeremy W;Wagener, John F;Ghribi, Othman;Geiger, Jonathan D
高水平的血清胆固醇和血脑屏障（BBB）的破坏都被认为是阿尔茨海默病发病机制的潜在机制。在动物和人类身上进行的研究结果表明，咖啡因可能对阿尔茨海默病有保护作用，但机制尚不清楚。我们用高胆固醇饮食的兔子来测试我们的假设，即长期摄入咖啡因可以防止高胆固醇饮食引起的血脑屏障破坏。研究人员给新西兰兔喂食富含2%胆固醇的饲料，并在饮水中添加3 mg咖啡因，连续12周。测量了血液中总胆固醇和咖啡因的浓度。使用组织学、免疫染色和免疫印迹技术评估嗅球（以及海马和大脑皮层的一些研究）的血脑屏障泄漏、血脑屏障紧密连接蛋白表达水平、星形胶质细胞激活和小胶质细胞密度。我们发现咖啡因阻断了高胆固醇饮食引起的IgG和纤维蛋白原外渗的增加，Evan蓝染料外渗的增加，紧密连接蛋白occludin和ZO-1水平的降低，星形胶质细胞激活和小胶质细胞密度的增加，其中IgG外渗存在。长期摄入咖啡因可以防止高胆固醇饮食引起的血脑屏障破坏增加，咖啡因和类似咖啡因的药物可能对治疗阿尔茨海默病有用。
High levels of serum cholesterol and disruptions of the blood brain barrier (BBB) have all been implicated as underlying mechanisms in the pathogenesis of Alzheimer's disease. Results from studies conducted in animals and humans suggest that caffeine might be protective against Alzheimer's disease but by poorly understood mechanisms. Using rabbits fed a cholesterol-enriched diet, we tested our hypothesis that chronic ingestion of caffeine protects against high cholesterol diet-induced disruptions of the BBB. New Zealand rabbits were fed a 2% cholesterol-enriched diet, and 3 mg caffeine was administered daily in drinking water for 12 weeks. Total cholesterol and caffeine concentrations from blood were measured. Olfactory bulbs (and for some studies hippocampus and cerebral cortex as well) were evaluated for BBB leakage, BBB tight junction protein expression levels, activation of astrocytes, and microglia density using histological, immunostaining and immunoblotting techniques. We found that caffeine blocked high cholesterol diet-induced increases in extravasation of IgG and fibrinogen, increases in leakage of Evan's blue dye, decreases in levels of the tight junction proteins occludin and ZO-1, increases in astrocytes activation and microglia density where IgG extravasation was present. Chronic ingestion of caffeine protects against high cholesterol diet-induced increases in disruptions of the BBB, and caffeine and drugs similar to caffeine might be useful in the treatment of Alzheimer's disease.