Department of Pharmacology and Therapeutic Chemistry. Institut de Neurociències-University of Barcelona, Avda. Joan XXIII, 27. 08028 Barcelona, Spain.
Department of Cellular and Molecular Biology, University Center of Biological and Agricultural Sciences, University of Guadalajara, km 15.5 Guadalajara-Nogales highway, C.P. 45110 Zapopan, Jalisco, Mexico.
Int J Mol Sci. 2019 Mar 6;20(5):1134. doi: 10.3390/ijms20051134.
A variety of environmental factors contribute significantly to age-related cognitive decline and memory impairment in Alzheimer's Disease (AD) and other neurodegenerative diseases. Nutrition can alter epigenetics, improving health outcomes, which can be transmitted across generations; this process is called epigenetic inheritance. We investigate the beneficial effects of maternal resveratrol supplementation in the direct exposed F1 generation and the transgenerational F2 generation. The offspring was generated from females Senescence Accelerated Mouse-Prone (SAMP8) fed a resveratrol-enriched diet for two months prior to mating. Object novel recognition and Morris Water Maze (MWM) demonstrated improvements in cognition in the 6-month-old F1 and F2 generations from resveratrol fed mothers. A significant increase in global DNA methylation with a decrease in hydroxymethylation in F1 and F2 were found. Accordingly, and gene expression changed. Methylation levels of and genes promoters raised in offspring, inducing changes in target genes expression, as well as hydrogen peroxide levels. Offspring that resulted from a resveratrol fed mother showed increase AMPKα activation, mTOR inhibition, and an increase in gene expression and Beclin-1 protein levels. Endoplasmic reticulum stress sensors were found changed both in F1 and F2 generations. Overall, our results demonstrated that maternal resveratrol supplementation could prevent cognitive impairment in the SAMP8 mice offspring through epigenetic changes and cell signaling pathways.
各种环境因素对阿尔茨海默病（AD）和其他神经退行性疾病相关的认知能力下降和记忆力减退有重要影响。营养可以改变表观遗传学，改善健康结果，并可以在代际之间传递；这个过程被称为表观遗传遗传。我们研究了母体白藜芦醇补充对直接暴露的 F1 代和跨代 F2 代的有益影响。后代是由雌性快速衰老加速小鼠品系（SAMP8）产生的，这些雌性在交配前两个月接受富含白藜芦醇的饮食。物体新颖性识别和 Morris 水迷宫（MWM）表明，来自接受白藜芦醇喂养的母亲的 6 个月大的 F1 和 F2 代在认知方面有所改善。在 F1 和 F2 中发现了全基因组 DNA 甲基化水平的显著增加和羟甲基化水平的降低。相应地，和 基因的表达发生了变化。在后代中， 和 基因启动子的甲基化水平升高，导致靶基因表达的变化，以及过氧化氢水平的升高。来自接受白藜芦醇喂养的母亲的后代表现出 AMPKα 激活增加、mTOR 抑制以及 基因表达和 Beclin-1 蛋白水平增加。内质网应激传感器在 F1 和 F2 两代中都发生了变化。总的来说，我们的结果表明，母体白藜芦醇补充可以通过表观遗传变化和细胞信号通路预防 SAMP8 小鼠后代的认知障碍。
