Metabolic Stress Induces Cognitive Disturbances and Inflammation in Aged Mice: Protective Role of Resveratrol

Palomera-Ávalos, Verónica; Griñán-Ferré, Christian; Izquierdo, Vanesa; Camins, Antoni; Sanfeliu, Coral; Pallàs, Mercè

doi:10.1089/rej.2016.1885

Cited by 47 publications

(45 citation statements)

References 50 publications

(56 reference statements)

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“…We have previously described that resveratrol dietary supplementation induced changes in cognition and molecular pathways in the hippocampus of aged [41,42] and AD mice models [43,44]. Here, we reported that body weight remained unchanged in the offspring from females supplemented with resveratrol before pregnancy in comparison with the sex control group, confirming the same effect in both sexes elicited by polyphenol, and corroborating previous studies [45,46].…”

Section: Discussionsupporting

confidence: 91%

Maternal Resveratrol Supplementation Prevents Cognitive Decline in Senescent Mice Offspring

Izquierdo¹,

Palomera-Ávalos²,

López-Ruiz³

et al. 2019

Preprint

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A variety of environmental factors contribute significantly to age-related cognitive decline and Alzheimer’s Disease (AD). Nutrition can alter epigenetics, improving health outcomes, which transmitted across generations; this process is called epigenetic inheritance. We investigate the beneficial effects of maternal resveratrol supplementation in offspring. We feed females SAMP8 with resveratrol-enriched diet during two months prior to mating. Direct exposed F1 generation and the transgenerational F2 generation were investigated. Object novel recognition and Morris water maze 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 resulted from 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.

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Section: Discussionsupporting

confidence: 91%

Maternal Resveratrol Supplementation Prevents Cognitive Decline in Senescent Mice Offspring

Izquierdo¹,

Palomera-Ávalos²,

López-Ruiz³

et al. 2019

Preprint

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“…SIRT1 can regulate mitochondrial biogenesis, contributing to the maintenance of functional mitochondria [107]. It is also well-established that SIRT1 regulates the activity and acetylation status of PGC-1α [103,108,109], and many studies have pointed out the ability of resveratrol to upregulate PGC-1α activity [110], which results in beneficial changes in the mitochondrial function [100,111,112]. Previous studies indicate the deficiencies of mitochondrial complexes in 3xTg-AD mice [54] and elevated levels of oxidative lesions and alterations of antioxidant enzymes [52,113].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Induces Brain Resilience Against Alzheimer Neurodegeneration Through Proteostasis Enhancement

et al. 2018

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Resveratrol is a natural compound that mimics the antioxidant and antiaging effects of caloric restriction, mainly mediated through SIRT1, a deacetylase that induces longevity and neuroprotection. We aimed to analyze the effects of resveratrol on the brain status of control non-transgenic (NoTg) and AD transgenic (3xTg-AD) mice to discern the mechanisms involved in a potential inducement of resilience against age-related neurodegeneration and Alzheimer's disease (AD). Mice were fed with a diet supplemented with 100 mg/kg of resveratrol from 2 months of age during 10 months. Resveratrol administration induced complete protection against memory loss and brain pathology in 3xTg-AD mice, and also induced cognitive enhancement in healthy NoTg mice. Resveratrol improved exploration and reduced anxiety in both mouse strains, indicative of well-being. Resveratrol reduced the presence of Aβ and p-tau pathology in the hippocampus of the 3xTg-AD mouse. Proteostasis analysis showed the following in both NoTg and 3xTg-AD mice: (i) increased levels of the amyloid-degrading enzyme neprilysin, (ii) reduction of the amyloidogenic secretase BACE1, and (iii) increase of proteasome protein levels and enhancement of proteasome activity. Resveratrol also increased AMPK protein levels, then upregulating the SIRT1 pathway, as shown by the activation of PGC-1α and CREB in both mice, resulting in further beneficial changes. Our data demonstrated that resveratrol induces cognitive enhancement and neuroprotection against amyloid and tau pathologies. Improvement of proteostasis by resveratrol, in both healthy and AD mice, suggests that it is a mechanism of brain resilience and defense against neurodegeneration caused by the accumulation of aberrant proteins.

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“…It has shown protective effects in a number of physiological and pathological processes due to its functions in metabolism, stress resistance and genomic stability (Haigis and Guarente, 2006). It is of note that the role of SIRT1 is linked with various proteins which modulating stress response or neuronal apoptosis in Aβ-treated models and age-related diseases (Kumar et al, 2016; Palomera-Ávalos et al, 2017). …”

Section: Introductionmentioning

confidence: 99%

Early-Life Exposure to Lead Induces Cognitive Impairment in Elder Mice Targeting SIRT1 Phosphorylation and Oxidative Alterations

Zhang

Wang

et al. 2017

Front. Physiol.

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Pb is a potential risk factor for cognition, mainly mediated by enhanced oxidative stress. Resveratrol, a natural polyphenol with crucial anti-oxidative property, is recently implicated in preventing cognitive deficits in normal aging and neurodegenerative disorders. Its beneficial effects have been linked to sirtuin 1(SIRT1) activation. The aim of this work is to investigate the possible linkage between alterations in Pb-induced oxidative damage and cognitive impairment by prolonged treatment of resveratrol. Male C57BL/6 mice were given Pb(Ac)2 treatment or deionized H2O for 12 weeks, and subjected to resveratrol gavage at the dose of 50 mg/kgBw•d or vehicle after Pb exposure. Results from biochemical analysis and immunohistofluorescence showed that Pb induced oxidative DNA damage and decreased cortical antioxidant biomarker. As expected, these abnormalities were improved by resveratrol treatment. Morris water maze test, Western blotting, immunohistofluorescence staining and RT-qPCR indicated that resveratrol ameliorated spatial learning and memory deficits with alterations in hippocampal BDNF-TrkB signaling, promoted nuclear localization and phosphorylation of hippocampal SIRT1, partly increased protein levels of AMPK and PGC-1α involving in modulation of antioxidant response in Pb-exposed mice. Our results support the hypothesis that resveratrol could attenuate Pb-induced cognitive impairment which was associated with activating SIRT1 via modulation of oxidative stress. Additionally, resveratrol also repressed the Pb-induce amyloidogenic processing with resultant decline in cortical Aβ1−−40. Noteworthy, such effects were not mediated by resveratrol treatment alone. These findings emphasize the potential of SIRT1 activator as an efficacious dietary intervention to downgrade the Pb-induced neurotoxic lesion.

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Metabolic Stress Induces Cognitive Disturbances and Inflammation in Aged Mice: Protective Role of Resveratrol

Cited by 47 publications

References 50 publications

Maternal Resveratrol Supplementation Prevents Cognitive Decline in Senescent Mice Offspring

Maternal Resveratrol Supplementation Prevents Cognitive Decline in Senescent Mice Offspring

Resveratrol Induces Brain Resilience Against Alzheimer Neurodegeneration Through Proteostasis Enhancement

Early-Life Exposure to Lead Induces Cognitive Impairment in Elder Mice Targeting SIRT1 Phosphorylation and Oxidative Alterations

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