Maternal Resveratrol Supplementation Prevents Cognitive Decline in Senescent Mice Offspring

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.

Lifestyle Modifications and Nutritional Interventions in Aging-Associated Cognitive Decline and Alzheimer’s Disease

“…Resveratrol activates a transcriptional coactivator, PGC-1α, that promotes energy metabolism by glucose uptake and mitochondrial biogenesis (Lagouge et al, 2006;Kumar and Lombard, 2015;Parihar et al, 2015). Recent studies have demonstrated that maternal resveratrol supplementation and vitamin D combined with resveratrol could prevent cognitive impairment in SAMP8 mice offspring through amyloidogenic pathways, neuroinflammation, tau phosphorylation, epigenetic changes, and cell signaling pathways (Cheng et al, 2017;Izquierdo et al, 2019). Another study indicated the ameliorative action of resveratrol in hippocampal neurodegeneration and memory performance (Gomes et al, 2018).…”

Resveratrol intake during pregnancy and lactation re-programs adiposity and ameliorates leptin resistance in male progeny induced by maternal high-fat/high sucrose plus postnatal high-fat/high sucrose diets via fat metabolism regulation

“…The influence of maternal resveratrol supplementation on progeny has also been discovered recently. It has been shown that maternal resveratrol therapy can prevent cognitive decline in senescent mice progeny [52]. Tanaka et al recently reported that prenatal resveratrol administration during lactation could decrease liver fatty acid synthesis of adult male rat progeny [53].…”

Epigenetics: Recent Advances and Its Role in the Treatment of Alzheimer's Disease

“…The supplementation of folic acid, a methyl donor, improves cognitive functions in participants who tend to decline with age (165). Interestingly, maternal supplementation of resveratrol promotes cognitive decline in the SAMP8 mice offspring via increasing global methylation levels and decreasing hydroxymethylation levels (166). Consequently, the DNA methyltransferase or the methyl donor may be potential treatments for patients with AD.…”