Abstract
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, Dnmt3a/b and Tet2 gene expression changed. Methylation levels of Nrf2 and NF-kβ 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 Pgc-1α 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.
Highlights
Age-related cognitive decline, especially memory impairment, is one of the most prevalent consequences of growing older [1]
We focus on Oxidative Stress (OS), neuroinflammation, Endoplasmic Reticulum (ER) stress, and monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin cascade signaling
Consistent with our new findings, it has been reported that the neuroprotective effects of resveratrol, against cognitive impairment induced by prenatal stress in the offspring of Wistar rats [43]
Summary
Age-related cognitive decline, especially memory impairment, is one of the most prevalent consequences of growing older [1]. Mounting evidence indicates that various environmental factors can modulate expression profiles of several genes through epigenetic programs that might modify the susceptibility and variability in the trajectory of age-related cognitive decline and AD [9]. Few studies have attempted to investigate beneficial nutrition outcomes following exposure to a resveratrol maternal diet Accepting these limitations, recent studies have demonstrated that maternal methyl supplements in mice change 5-mC in offspring [13] and maternal high-fat diet exposure promotes histone modifications in neonatal rats [14]. Epigenetic changes have been associated with accelerated ageing in SAMP8 [25,26], and several studies demonstrated that environmental interventions induced changes in the epigenome, reducing cognitive impairment [25,27]. Tfeemsta(lNe OF2RgTr)oiunpf:e&m&a&le&s pan
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