Resveratrol supplementation confers neuroprotection in cortical brain tissue of nonhuman primates fed a high-fat/sucrose diet.
Resveratrol supplementation confers neuroprotection in cortical brain tissue of nonhuman primates fed a high-fat/sucrose diet.
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DOI：
10.18632/aging.100942
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发表时间：
2016-05
期刊：
影响因子：
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通讯作者：
de Cabo R
中科院分区：
文献类型：
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作者：
Bernier M;Wahl D;Ali A;Allard J;Faulkner S;Wnorowski A;Sanghvi M;Moaddel R;Alfaras I;Mattison JA;Tarantini S;Tucsek Z;Ungvari Z;Csiszar A;Pearson KJ;de Cabo R
以往的研究表明，长期补充白藜芦醇(RSV)在预防高脂/高糖(HFS)饮食引起的非人灵长类动物胰岛β细胞功能障碍、动脉硬化和代谢下降方面具有积极作用。在这里，分析扩展到检查RSV是否可以减少同一组受试动物大脑皮层的饮食应激毒性。用HFS单独或与RSV联合喂养中年雄性恒河猴2年后，对大脑皮层组织进行全基因组芯片分析，同时进行ELISA法、免疫荧光和生化分析，以检测大脑皮层血管健康和炎症的标志物。在这些饮食干预中差异调节的一些基因和途径表明，高铁饲料喂养的动物的神经炎症(例如，氧化应激标志物、细胞凋亡、核因子-κB激活)加剧，并通过呼吸道合胞病毒治疗进行保护。补充RSV可减轻HFS应激所致的线粒体乙醛脱氢酶2表达下降、内皮型一氧化氮合酶表达紊乱和毛细血管密度降低。我们的结果表明，长期的RSV治疗对营养应激期间的脑血管功能障碍具有神经保护作用。
Previous studies have shown positive effects of long-term resveratrol (RSV) supplementation in preventing pancreatic beta cell dysfunction, arterial stiffening and metabolic decline induced by high-fat/high-sugar (HFS) diet in nonhuman primates. Here, the analysis was extended to examine whether RSV may reduce dietary stress toxicity in the cerebral cortex of the same cohort of treated animals. Middle-aged male rhesus monkeys were fed for 2 years with HFS alone or combined with RSV, after which whole-genome microarray analysis of cerebral cortex tissue was carried out along with ELISA, immunofluorescence, and biochemical analyses to examine markers of vascular health and inflammation in the cerebral cortices. A number of genes and pathways that were differentially modulated in these dietary interventions indicated an exacerbation of neuroinflammation (e.g., oxidative stress markers, apoptosis, NF-κB activation) in HFS-fed animals and protection by RSV treatment. The decreased expression of mitochondrial aldehyde dehydrogenase 2, dysregulation in endothelial nitric oxide synthase, and reduced capillary density induced by HFS stress were rescued by RSV supplementation. Our results suggest that long-term RSV treatment confers neuroprotection against cerebral vascular dysfunction during nutrient stress.