scholarly journals Dietary Polyphenols as Modulators of Brain Functions: Biological Actions and Molecular Mechanisms Underpinning Their Beneficial Effects

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
David Vauzour
Keyword(s):  
Cognitive Function ◽  
Molecular Mechanisms ◽  
Inflammatory Stress ◽  
Dietary Polyphenols ◽  
Beneficial Effects ◽  
Brain Functions ◽  
Expression Of Genes ◽  
Age Related ◽  
Neuroprotective Actions ◽  
Protective Signaling

Accumulating evidence suggests that diet and lifestyle can play an important role in delaying the onset or halting the progression of age-related health disorders and to improve cognitive function. In particular, polyphenols have been reported to exert their neuroprotective actions through the potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning, and cognitive function. Despite significant advances in our understanding of the biology of polyphenols, they are still mistakenly regarded as simply acting as antioxidants. However, recent evidence suggests that their beneficial effects involve decreases in oxidative/inflammatory stress signaling, increases in protective signaling and neurohormetic effects leading to the expression of genes that encode antioxidant enzymes, phase-2 enzymes, neurotrophic factors, and cytoprotective proteins. Specific examples of such pathways include the sirtuin-FoxO pathway, the NF-κB pathway, and the Nrf-2/ARE pathway. Together, these processes act to maintain brain homeostasis and play important roles in neuronal stress adaptation and thus polyphenols have the potential to prevent the progression of neurodegenerative pathologies.

scholarly journals Resveratrol Attenuates Copper-Induced Senescence by Improving Cellular Proteostasis

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Liliana Matos ◽  
Alexandra Monteiro Gouveia ◽  
Henrique Almeida
Keyword(s):  
Molecular Mechanisms ◽  
Protein Quality ◽  
Replicative Senescence ◽  
Beneficial Effects ◽  
Cell Dysfunction ◽  
Age Related ◽  
Cell Tissue ◽  
Autophagy Induction ◽  
Human Disorders ◽  
Senescence Associated Genes

Copper sulfate-induced premature senescence (CuSO4-SIPS) consistently mimetized molecular mechanisms of replicative senescence, particularly at the endoplasmic reticulum proteostasis level. In fact, disruption of protein homeostasis has been associated to age-related cell/tissue dysfunction and human disorders susceptibility. Resveratrol is a polyphenolic compound with proved antiaging properties under particular conditions. In this setting, we aimed to evaluate resveratrol ability to attenuate cellular senescence induction and to unravel related molecular mechanisms. Using CuSO4-SIPS WI-38 fibroblasts, resveratrol is shown to attenuate typical senescence alterations on cell morphology, senescence-associated beta-galactosidase activity, and cell proliferation. The mechanisms implicated in this antisenescence effect seem to be independent of senescence-associated genes and proteins regulation but are reliant on cellular proteostasis improvement. In fact, resveratrol supplementation restores copper-induced increased protein content, attenuates BiP level, and reduces carbonylated and polyubiquitinated proteins by autophagy induction. Our data provide compelling evidence for the beneficial effects of resveratrol by mitigating CuSO4-SIPS stressful consequences by the modulation of protein quality control systems. These findings highlight the importance of a balanced cellular proteostasis and add further knowledge on molecular mechanisms mediating resveratrol antisenescence effects. Moreover, they contribute to identifying specific molecular targets whose modulation will prevent age-associated cell dysfunction and improve human healthspan.

scholarly journals Age-specific gene signatures underlying the transcriptomes and functional connectomes of human cerebral cortex

2020 ◽  
Author(s):  
Xingzhong Zhao ◽  
Jingqi Chen ◽  
Peipei Xiao ◽  
Jianfeng Feng ◽  
Ning Qing ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Molecular Mechanisms ◽  
Early Adulthood ◽  
Structural Features ◽  
Magnetic Resonance Images ◽  
Specific Gene ◽  
Human Cerebral Cortex ◽  
Gene Signatures ◽  
Brain Functions ◽  
Age Related

AbstractThe human cerebral cortex undergoes profound structural and functional dynamic variations across the lifespan, whereas the underlying molecular mechanisms remain unclear. Here, with a novel method TCA (Transcriptome-connectome Correlation Analysis), which integrates the brain functional MR magnetic resonance images and region-specific transcriptomes, we identify age-specific cortex (ASC) gene signatures for adolescence, early adulthood, and late adulthood. The ASC gene signatures are significantly correlated with the cortical thickness (P-value <2.00e-3) and myelination (P-value <1.00e-3), two key brain structural features that vary in accordance with brain development. In addition to the molecular underpinning of age-related brain functions, the ASC gene signatures allow delineation of the molecular mechanisms of neuropsychiatric disorders, such as the regulation between ARNT2 and its target gene ETF1 involved in Schizophrenia. We further validate the ASC gene signatures with published gene sets associated with the adult cortex, and confirm the robustness of TCA on other brain image datasets.

scholarly journals Superior Effects of Modified Chen-Style Tai Chi versus 24-Style Tai Chi on Cognitive Function, Fitness, and Balance Performance in Adults over 55

2019 ◽  
Vol 9 (5) ◽  
pp. 102 ◽  
Author(s):  
Liye Zou ◽  
Paul D. Loprinzi ◽  
Jane Jie Yu ◽  
Lin Yang ◽  
Chunxiao Li ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Function ◽  
Tai Chi ◽  
Dynamic Balance ◽  
Aging Population ◽  
Balance Performance ◽  
Timed Up And Go ◽  
Beneficial Effects ◽  
Global Cognitive Function ◽  
Age Related

Background: Cognitive decline and balance impairment are prevalent in the aging population. Previous studies investigated the beneficial effects of 24-style Tai Chi (TC-24) on either cognitive function or balance performance of older adults. It still remains largely unknown whether modified Chen-style TC (MTC) that includes 18 complex movements is more beneficial for these age-related health outcomes, as compared to TC-24. Objective: We investigated if MTC would show greater effects than TC-24 on global cognitive function and balance-related outcomes among older adults. Methods: We conducted a randomized trial where 80 eligible adults aged over 55 were allocated into two different styles of Tai Chi (TC) arms (sixty-minute session × three times per week, 12 weeks). Outcome assessments were performed at three time periods (baseline, Week 6, and Week 12) and included the Chinese Version of the Montreal Cognitive Assessment (MoCA) for overall cognitive function, One-leg Standing Test (LST) for static balance, Timed Up and Go Test (TUGT) for dynamic balance, chair Stand Test (CST) for leg power, and the six-meter Walk Test (6MWT) for aerobic exercise capacity. Results: Compared to TC-24 arm, MTC arm demonstrated significantly greater improvements in MoCA, LST, TUGT, CST, and 6MWT (all p < 0.05). Conclusions: Both forms of TC were effective in enhancing global cognitive function, balance, and fitness. Furthermore, MTC was more effective than TC-24 in enhancing these health-related parameters in an aging population.

scholarly journals Molecular Mechanisms Underlying the Beneficial Effects of Exercise on Brain Function and Neurological Disorders

2021 ◽  
Vol 22 (8) ◽  
pp. 4052
Author(s):  
Kévin Nay ◽  
William J. Smiles ◽  
Jacqueline Kaiser ◽  
Luke M. McAloon ◽  
Kim Loh ◽  
...  
Keyword(s):  
Brain Function ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Well Being ◽  
Developed Countries ◽  
Beneficial Effects ◽  
Therapeutic Benefits ◽  
Age Related ◽  
Underlying Mechanisms ◽  
The Impact

As life expectancy has increased, particularly in developed countries, due to medical advances and increased prosperity, age-related neurological diseases and mental health disorders have become more prevalent health issues, reducing the well-being and quality of life of sufferers and their families. In recent decades, due to reduced work-related levels of physical activity, and key research insights, prescribing adequate exercise has become an innovative strategy to prevent or delay the onset of these pathologies and has been demonstrated to have therapeutic benefits when used as a sole or combination treatment. Recent evidence suggests that the beneficial effects of exercise on the brain are related to several underlying mechanisms related to muscle–brain, liver–brain and gut–brain crosstalk. Therefore, this review aims to summarize the most relevant current knowledge of the impact of exercise on mood disorders and neurodegenerative diseases, and to highlight the established and potential underlying mechanisms involved in exercise–brain communication and their benefits for physiology and brain function.

scholarly journals Identifying age-specific gene signatures of the human cerebral cortex with joint analysis of transcriptomes and functional connectomes

2020 ◽  
Author(s):  
Xingzhong Zhao ◽  
Jingqi Chen ◽  
Peipei Xiao ◽  
Jianfeng Feng ◽  
Qing Nie ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Molecular Mechanisms ◽  
Magnetic Resonance Images ◽  
Joint Analysis ◽  
P Value ◽  
Specific Gene ◽  
Human Cerebral Cortex ◽  
Gene Signatures ◽  
Brain Functions ◽  
Age Related

Abstract The human cerebral cortex undergoes profound structural and functional dynamic variations across the lifespan, whereas the underlying molecular mechanisms remain unclear. Here, with a novel method transcriptome-connectome correlation analysis (TCA), which integrates the brain functional magnetic resonance images and region-specific transcriptomes, we identify age-specific cortex (ASC) gene signatures for adolescence, early adulthood and late adulthood. The ASC gene signatures are significantly correlated with the cortical thickness (P-value &lt;2.00e-3) and myelination (P-value &lt;1.00e-3), two key brain structural features that vary in accordance with brain development. In addition to the molecular underpinning of age-related brain functions, the ASC gene signatures allow delineation of the molecular mechanisms of neuropsychiatric disorders, such as the regulation between ARNT2 and its target gene ETF1 involved in Schizophrenia. We further validate the ASC gene signatures with published gene sets associated with the adult cortex, and confirm the robustness of TCA on other brain image datasets. Availability: All scripts are written in R. Scripts for the TCA method and related statistics result can be freely accessed at https://github.com/Soulnature/TCA. Additional data related to this paper may be requested from the authors.

scholarly journals Procaine–The Controversial Geroprotector Candidate: New Insights Regarding Its Molecular and Cellular Effects

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Daniela Gradinaru ◽  
Anca Ungurianu ◽  
Denisa Margina ◽  
Maria Moreno-Villanueva ◽  
Alexander Bürkle
Keyword(s):  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
Experimental Models ◽  
Beneficial Effects ◽  
Cellular Effects ◽  
Treatment And Prevention ◽  
Age Related ◽  
Myocardial Ischemia Reperfusion

Since its discovery in 1905 and its employment in everyday medical practice as a local anesthetic, to its highly controversial endorsement as an “anti-aging” molecule in the sixties and seventies, procaine is part of the history of medicine and gerontoprophylaxis. Procaine can be considered a “veteran” drug due to its long-time use in clinical practice, but is also a molecule which continues to incite interest, revealing new biological and pharmacological effects within novel experimental approaches. Therefore, this review is aimed at exploring and systematizing recent data on the biochemical, cellular, and molecular mechanisms involved in the antioxidant and potential geroprotective effects of procaine, focusing on the following aspects: (1) the research state-of-the-art, through an objective examination of scientific literature within the last 30 years, describing the positive, as well as the negative reports; (2) the experimental data supporting the beneficial effects of procaine in preventing or alleviating age-related pathology; and (3) the multifactorial pathways procaine impacts oxidative stress, inflammation, atherogenesis, cerebral age-related pathology, DNA damage, and methylation. According to reviewed data, procaine displayed antioxidant and cytoprotective actions in experimental models of myocardial ischemia/reperfusion injury, lipoprotein oxidation, endothelial-dependent vasorelaxation, inflammation, sepsis, intoxication, ionizing irradiation, cancer, and neurodegeneration. This analysis painted a complex pharmacological profile of procaine: a molecule that has not yet fully expressed its therapeutic potential in the treatment and prevention of aging-associated diseases. The numerous recent reports found demonstrate the rising interest in researching the multiple actions of procaine regulating key processes involved in cellular senescence. Its beneficial effects on cell/tissue functions and metabolism could designate procaine as a valuable candidate for the well-established Geroprotectors database.

scholarly journals Effect of Polyphenols on Cognitive Function: Evidence from Population-based Studies and Clinical Trials

2021 ◽  
Author(s):  
Wenzhe Yang ◽  
Kaiwang Cui ◽  
X. Li ◽  
J. Zhao ◽  
Z. Zeng ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cognitive Function ◽  
Population Aging ◽  
Disease Onset ◽  
Epidemiological Data ◽  
Human Beings ◽  
Cross Sectional ◽  
Dietary Polyphenols ◽  
Age Related

AbstractDue to progressive population aging, a new dementia case occurs at every 3 seconds, placing a heavy burden of disease. Identifying potential risk or preventive factors is emphasized owing to a lack of effective treatment for dementia. There has been emerging evidence on the link of certain dietary components, particularly polyphenols, to brain wellness and cognitive outcomes. Findings from animal and in vitro studies appear more consistent and conclusive. However, such an association has not been investigated in depth in human beings. In this review, we examined studies on the effect of dietary polyphenols (including flavonoids, curcumin, and resveratrol) on cognitive function. Intervention in early stages of dementia/Alzheimer’s disease might be a target to slow down age-related cognitive decline before disease onset. We summarized 28 epidemiological studies (8 cross-sectional and 20 cohort studies) and 55 trials in this review. Preliminary evidence from epidemiological data provides the necessity for intervention trials, even though the measures of polyphenol intake tend to be less precise. Clinical trials are in favor of the role of some polyphenols in benefiting specific domains of cognition. This review also describes the divergence of results and current limitations of research in this field.

scholarly journals γ-Oryzanol Improves Cognitive Function and Modulates Hippocampal Proteome in Mice

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 753 ◽  
Author(s):  
Wiramon Rungratanawanich ◽  
Giovanna Cenini ◽  
Andrea Mastinu ◽  
Marc Sylvester ◽  
Anne Wilkening ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Brain Function ◽  
Clinical Symptoms ◽  
Oryza Sativa L ◽  
Beneficial Effects ◽  
Adult Mice ◽  
Age Related ◽  
Y Maze ◽  
Quantitative Changes

Rice (Oryza sativa L.) is the richest source of γ-oryzanol, a compound endowed with antioxidant and anti-inflammatory properties. γ-Oryzanol has been demonstrated to cross the blood-brain barrier in intact form and exert beneficial effects on brain function. This study aimed to clarify the effects of γ-oryzanol in the hippocampus in terms of cognitive function and protein expression. Adult mice were administered with γ-oryzanol 100 mg/kg or vehicle (control) once a day for 21 consecutive days following which cognitive behavior and hippocampal proteome were investigated. Cognitive tests using novel object recognition and Y-maze showed that long-term consumption of γ-oryzanol improves cognitive function in mice. To investigate the hippocampal proteome modulated by γ-oryzanol, 2D-difference gel electrophoresis (2D-DIGE) was performed. Interestingly, we found that γ-oryzanol modulates quantitative changes of proteins involved in synaptic plasticity and neuronal trafficking, neuroprotection and antioxidant activity, and mitochondria and energy metabolism. These findings suggested γ-oryzanol as a natural compound able to maintain and reinforce brain function. Although more intensive studies are needed, we propose γ-oryzanol as a putative dietary phytochemical for preserving brain reserve, the ability to tolerate age-related changes, thereby preventing clinical symptoms or signs of neurodegenerative diseases.

scholarly journals Bioactive Polyphenols and Neuromodulation: Molecular Mechanisms in Neurodegeneration

2020 ◽  
Vol 21 (7) ◽  
pp. 2564 ◽  
Author(s):  
Francesco Di Meo ◽  
Anna Valentino ◽  
Orsolina Petillo ◽  
Gianfranco Peluso ◽  
Stefania Filosa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Web Of Science ◽  
Cellular Functions ◽  
Active Metabolites ◽  
Dietary Polyphenols ◽  
Age Related ◽  
Age Related Cognitive Decline ◽  
Preventive Effects

The interest in dietary polyphenols in recent years has greatly increased due to their antioxidant bioactivity with preventive properties against chronic diseases. Polyphenols, by modulating different cellular functions, play an important role in neuroprotection and are able to neutralize the effects of oxidative stress, inflammation, and apoptosis. Interestingly, all these mechanisms are involved in neurodegeneration. Although polyphenols display differences in their effectiveness due to interindividual variability, recent studies indicated that bioactive polyphenols in food and beverages promote health and prevent age-related cognitive decline. Polyphenols have a poor bioavailability and their digestion by gut microbiota produces active metabolites. In fact, dietary bioactive polyphenols need to be modified by microbiota present in the intestine before being absorbed, and to exert health preventive effects by interacting with cellular signalling pathways. This literature review includes an evaluation of the literature in English up to December 2019 in PubMed and Web of Science databases. A total of 307 studies, consisting of research reports, review articles and articles were examined and 146 were included. The review highlights the role of bioactive polyphenols in neurodegeneration, with a particular emphasis on the cellular and molecular mechanisms that are modulated by polyphenols involved in protection from oxidative stress and apoptosis prevention.

scholarly journals RL-118 and 11β-HSD1 target engagement through TAPS assay: behaviour and molecular analysis

2020 ◽  
Author(s):  
D. Puigoriol-Illamola ◽  
J. Companys-Alemany ◽  
N. Homer ◽  
R. Leiva ◽  
S. Vázquez ◽  
...  
Keyword(s):  
Cognitive Performance ◽  
Molecular Mechanisms ◽  
Target Engagement ◽  
App Processing ◽  
Beneficial Effects ◽  
Cognitive Improvement ◽  
Age Related ◽  
The One ◽  
Age Related Cognitive Decline ◽  
Samp8 Mice

1.AbstractTaking into consideration the convergence of ageing, stress and neurodegenerative diseases, such as AD, there is impaired GC signalling. Therefore, the study of GC-mediated stress response to chronic moderate stressful situations, as account in daily life, becomes of huge interest to design pharmacological strategies to prevent neurodegeneration.To address this issue, SAMP8 were exposed for 4 weeks to the CMS paradigm and treated with RL-118, an 11β-HSD1 inhibitor. In fact, several pieces of evidence link the inhibition of this enzyme with reduction of GC levels and cognitive improvement, while CMS exposure has been associated with reduced cognitive performance. The aim of this project was to assess whether RL-118 treatment could restore the deleterious effects of CMS on cognition and behavioural abilities, but also on molecular mechanisms that compromise healthy ageing in SAMP8 mice.On the one hand, we determined the target engagement between RL-118 and 11β-HSD1. Therefore all the beneficial effects previously described in SAMP8 treated with the drug can undoubtedly be attributed to the inhibition of this enzyme. Besides, herein we observed decreased DNA methylation, hydroxymethylation and histone phosphorylation induced by CMS but, on the contrary, increased after RL-118 treatment. In addition, CMS exposure produced ROS damage accumulation, and increments of pro-oxidant enzymes as well as pro-inflammatory mediators through NF-κB pathway and astrogliosis markers, like Gfap. Of note, those modifications were recovered by 11β-HSD1 inhibition. Remarkably, although CMS altered mTORC1 signalling, autophagy was increased in SAMP8 treated with RL-118 mice. Also, we found amyloidogenic APP processing pathway favoured and decreased synaptic plasticity and neuronal remodelling markers in mice under CMS, but changed after RL-118 treatment. In consequence, detrimental effects on behaviour and cognitive performance were detected in CMS exposed mice, but restored after concomitant 11β-HSD1 inhibition by RL-118.Overall, CMS is a feasible intervention to understand the influence of stress on epigenetic mechanisms underlying cognition and accelerating senescence. However and most important, 11β-HSD1 inhibition through RL-118 turned up to restore the majority of these detrimental effects caused by CMS, indicating that GC excess attenuation may become a potential therapeutic strategy for age-related cognitive decline and AD.

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