Abstract
Environmental factors such as maternal high-fat diet (HFD) intake can increase the risk of age-related cognitive decline in adult offspring. Epigenetic mechanisms are a possible link between diet effect and neurodegeneration across generations. Here, we found a significant decrease in triglyceride levels in a high-fat diet with resveratrol (RSV) HFD + RSV group and the offspring. Firstly, we obtained better cognitive performance in HFD+RSV groups and their offspring. Molecularly, a significant increase in DNA methylation (5-mC) levels, as well as increased gene expression of DNA methyltransferase 1 (Dnmt1) and Dnmt3a in HFD + RSV F1 group, were found. Furthermore, a significant increase of N6-Methyladenosine methylation (m6A) levels in HFD+RSV F1, as well as changes in gene expression of its enzymes Methyltransferase like 3 (Mettl3) and FTO alpha-ketoglutarate dependent dioxygenase (Fto) were found. Moreover, we found a decrease in gene expression levels of pro-inflammatory markers such as Interleukin 1β (Il1-β), Interleukin 6 (Il-6), Tumor necrosis factor-α (Tnf-α), C-X-C motif chemokine ligand 10 (Cxcl-10), the pro-inflammatory factors monocyte chemoattractant protein 1 (Mcp-1) and Tumor growth factor-β1 (Tgf-β1) in HFD+RSV and HFD+RSV F1 groups. Moreover, there was increased gene expression of neurotrophins such as Neural growth factor (Ngf), Neurotrophin-3 (Nt3), and its receptors Tropomyosin receptor kinase TrkA and TrkB. Likewise, an increase in protein levels of brain-derived neurotrophic factor (BDNF) and phospho-protein kinase B (p-Akt) in HFD+RSV F1 was found. These results suggest that maternal RSV supplementation under HFD intake prevents cognitive decline in senescence-accelerated mice prone 8 (SAMP8) adult offspring, promoting a reduction in triglycerides and leptin plasma levels, changes in the pro-inflammatory profile, and restoring the epigenetic landscape as well as synaptic plasticity.
Highlights
Due to the advancing life expectancy in modern societies, research in aging-hallmarks leading to neurodegeneration and Alzheimer’s disease (AD), is an important scientific field [1]
We found a significant decreased TG levels in high-fat diet (HFD) senescence-accelerated mice prone 8 (SAMP8) mice directly supplemented with RSV (HFD +R SV group), and their offspring, compared to HFD mice in F1 (Figure 1C)
We found a significantly decreased gene expression for Il1-ß, Interleukin 6 (Il-6), C-XC motif chemokine ligand 10 (Cxcl-10), the pro-inflammatory factors monocyte chemoattractant protein 1 (Mcp-1), Transforming growth factor beta 1 (Tgf-ß1), and a significantly decreased for Tumor necrosis factor-α (Tnf-α) in the HFD + RSV compared to the HFD group (Figure 4A–F)
Summary
Due to the advancing life expectancy in modern societies, research in aging-hallmarks leading to neurodegeneration and Alzheimer’s disease (AD), is an important scientific field [1]. Aging has been linked to progressive brain deterioration, leading to impaired cognitive function, and increasing vulnerability to death [2]. This cognitive impairment is commonly accompanied by different molecular alterations like inflammation, synaptic dysfunction, and epigenetic modification, among others [3]. Pleiotropic compounds to rescue them is a significant field of research [4] In this regard, nutrition and supplementation are important components of healthy brain aging, in those with dementia [5]. Nutrition and supplementation are important components of healthy brain aging, in those with dementia [5] It is well-established that the consumption of a high-fat diet (HFD) increases the risk of several chronic diseases, including age-related cognitive decline [6]. The synaptic plasticity is primarily mediated by neurotrophins, among them, brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT3), allowing the permissive conditions under which plasticity can appear [11,12]
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