WAC 2022 banner
IVES 9 IVES Conference Series 9 WAC 9 WAC 2022 9 4 - WAC - Oral presentations 9 Epigenetic Modulation Of Inflammation And Synaptic Plasticity By Polyphenolic Metabolites Promotes Resilience Against Stress In Mice

Epigenetic Modulation Of Inflammation And Synaptic Plasticity By Polyphenolic Metabolites Promotes Resilience Against Stress In Mice

Abstract

Introduction: Major depressive disorder is associated with abnormalities in the brain and the immune system. Chronic stress in animals showed that epigenetic and inflammatory mechanisms play important roles in mediating resilience and susceptibility to depression.

Material & Methods: Here, through a high- throughput screening, we identify two phytochemicals, dihydrocaffeic acid (DHCA) and malvidin-3′-O-glucoside (Mal-gluc) that are effective in promoting resilience against stress by modulating brain synaptic plasticity and peripheral inflammation. DHCA/Mal-gluc also significantly reduces depression-like phenotypes in a mouse model of increased systemic inflammation induced by transplantation of hematopoietic progenitor cells from stress- susceptible mice.
Results: DHCA reduces pro-inflammatory interleukin 6 (IL-6) generations by inhibiting DNA methylation at the CpG-rich IL-6 sequences introns 1 and 3, while Mal-gluc modulates synaptic plasticity by increasing histone acetylation of the regulatory sequences of the Rac1 gene.

Conclusions:

This study suggests that polyphenolic metabolites capable of influencing peripheral inflammation and synaptic maladaptation may eventually be implemented as novel therapeutic interventions for promotion of mental health.

References

  1. Wang J, Gong B, Zhao W, Tang C, Varghese M, Nguyen T, Bi W, Bilski A, Begum S, Vempati P, Knable L, Ho L, Pasinetti GM. Epigenetic mechanisms linking diabetes and synaptic impairments. Diabetes 63(2):645-54 (2014).
  2. Herman F, Pasinetti GM. Principles of Inflammasome Priming and Inhibition: Implications for Psychiatric Disorders. Brain Behavior and Immunity DOI: 10.1016/j.bbi.2018.06.010 (2018).
  3. Herman F, Simkovic S, Pasinetti GM. The Neuroimmune Nexus of Depression and Dementia: Mechanisms and Targets. The British Journal of Pharmacology DOI: 10.1111/bph.14569 (2019).

DOI:

Publication date: June 14, 2022

Issue: WAC 2022

Type: Article

Tags

IVES Conference Series | WAC 2022

Citation

Related articles…

Modulation of berry composition by different vineyard management practices

High concentration of sugars in grapes and alcohol in wines is one of the consequences of climate change on viticulture production in several wine-growing regions. In order to investigate the possibilities of adaptation of vineyard management practices aimed to reduce the accumulation of sugar during the maturation phase without reducing the accumulation of anthocyanins in grapes, a study with severe shoot trimming, shoot thinning, cluster thinning and date of harvest was conducted on Merlot variety in Istria region (Croatia), under the Mediterranean climate. Four factors which may affect grape maturation and its composition at harvest were investigated in a two-years experiment; severe shoot trimming applied at veraison when >80% of berries changed colour (in comparison to untreated control), shoot thinning (0 and 30%), cluster thinning (0 and 30%), and the date of harvest (early and standard harvest dates). Shoot thinning had no significant impact on berry composition, despite the obtained reduction in yield per vine. Lower Brix in grapes were obtained with earlier harvest date and if no cluster thinning was applied, although at the same time a reduction in the concentration of anthocyanins in berries was observed in these treatments. On the other hand, if severe shoot trimming was applied when >80% of berries changed colour, a reduction of Brix was obtained without a negative impact on berry anthocyanins concentration. We conclude that in cases when undesirably high sugar concentrations at harvest are expected, severe shoot trimming at 80% veraison may effectively be used in order to obtain moderate sugar concentration in berries together with the adequate phenolic composition.

Climate change impacts on Douro Region viticulture and adaptation measures

Climate has a significant impact in the success of any agricultural system, with a direct influence on the crops suitability to a given region, interfering on yield and quality and also with the economic sustainability of the productive activity. In the Douro Demarcated Region (RDD), as in most regions of the Mediterranean climate, the scarce precipitation (33% has less than 600 mm per year), and your high variability, associated with high rates of evapotranspiration during the summer, is usually one of the fundamental factors that limit the grapevine development, as well as the production and quality of the harvest. Thus, facing the scenario in temperature changes for the next decades (1.5-2.5°C) and confirming the predictions of precipitation decreases and/or great variability in the occurrence of heat waves and intense rainfall, the consequences for slope stability in mountain viticulture and sustainability of all operations involved, are risks to be taken into account. In this way, a deepest and sustained knowledge regarding the adaptation measures to adverse environmental conditions is of a crucial importance, enabling a more efficient adaptation of plant growth conditions and the optimization of production and quality of the grapevines. The development of this work, carried out in two commercial vineyards, one located in Soutelo do Douro, São João da Pesqueira, Cima Corgo sub-region, and another located in Numão, Vila Nova de Foz Côa, Douro Superior sub-region, it seeks to establish a relationship between climatic elements and physiological, productive and qualitative parameters, as well as to evaluate the effectiveness of adaptation measures, including different types of deficit irrigation (2002-2019) and the application of shading nets (2019-2020) in the physiological, viticultural and oenological behavior in the Touriga Nacional and Moscatel Galego Branco varieties, respectively. The results showed that the application of deficit irrigation allowed to significantly reduce the impact of the adverse weather conditions at key moments in the development of the grapevine, particularly in the period immediately before veráison and maturation, reducing the negative effects on the physiological processes and productivity, without compromise the must quality parameters. On the other hand, the application of shading nets significantly reduced de leaves temperature, allowing to increase the water potential, stomatal conductance and photosynthetic rate of grapes, which was reflected in the yield increase in the 2nd year of the study. For the maturation indicators, higher levels of total acidity, malic acid and assimilable nitrogen were obtained. The last measure presents a huge potential, being essential to carry out more years of trials to obtain stronger conclusions in terms of production parameters, but also in characteristics as important as the grape ripening components and the organoleptic characteristics of wines.

Updating the Winkler index: An analysis of Cabernet sauvignon in Napa Valley’s varied and changing climate

This study aims to create an updated, agile viticultural climate index (similar to the Winkler Index) by performing in-depth analyses of current and historical data from industry partners in several major winegrowing regions. The Winkler Index was developed in the early twentieth century based on analysis of various grape-growing regions in California. The index uses heat accumulation (i.e. Growing Degree Days) throughout the growing season to determine which grape varieties are best suited to each region. As viticultural regions are increasingly subject to the complexity and uncertainty of a changing climate, a more rigorous, agile model is needed to aid grape growers in determining which cultivars to plant where. For the first phase of this study, 21 industry partners throughout Napa Valley shared historical phenology, harvest, viticultural practice, and weather data related to their Cabernet sauvignon vineyard blocks. To complement this data, berry samples were collected throughout the 2021 growing season from 50 vineyard blocks located throughout 16 American Viticultural Areas that were then analyzed for basic berry chemistry and phenolics. These blocks have been mapped using a Geographic Information System (GIS), enabling analysis of altitude, vineyard row orientation, slope, and remotely sensed climate data. Sampling sites were also chosen based on their proximity to a weather station. By analyzing historical data from industry partners and data specifically collected for this study, it is possible to identify key parameters for further analysis. Initial results indicate extreme variability at a high spatial resolution not currently accounted for in modern viticultural climate indices and suggest that viticultural practices play a major role. Using the structure of data collection and analyses developed for the first phase, this project will soon be expanded to other wine regions globally, while continuing data collection in Napa Valley.

Diagnosis of soil quality and evaluation of the impact of viticultural practices on soil biodiversity in a vineyard in southwestern France

Viticulture is facing two major changes – climate change and agroecological transition. In both cases, soil quality is seen as a lever to move towards a more sustainable viticulture. However, soil biological quality is little considered in the implementation of viticultural practices. Gascogn’Innov (2017-2022) is an Operational Group funded by the European Innovation Partnership for Agriculture. As such, it brings together winegrowers from the south-west of France, scientists, advisors and technicians, around a project focused on viticultural soil biological functioning and the design of technical routes more respectful toward soil heritage. To achieve this, the project aims to acquire references on the impact of viticultural practices on soil biology from a dynamic way, and to test a methodology to integrate information provided by the soil bioindicators to manage farming systems. A set of indicators of soil biological quality are evaluated in the project: microorganisms (bacteria and fungi abundance and diversity), fauna (abundance and diversity of nematodes and earthworms), physico-chemical characteristics, soil structure assessment and degradation rate of organic matter. Based on a network of 13 plots that have been subject to an initial diagnosis in 2017, several agronomical practices to restore soil fertility are experimented to redesign the cropping system (for instance plant cover, organic matter inputs, reduction of herbicides, mineral fertilizers). System redesign was made in collaboration by winegrowers and an interdisciplinary group of experts (agronomists, biologists). Several indicators are measured on vine and soil at each vintage to assess vine health and productivity. At the end of the project (2021), a final diagnosis was carried out. Gascogn’Innov allowed to create a regional database on the quality of wine-growing soils, which permitted to evaluate the effect of practices according to soil types. Especially, decreasing the intensity of tillage and increasing the duration and diversity of grass coverage tends to increase the abundance of all the organisms studied. This project confirmed the value of soil biological quality indicators to drive the sustainability of practices, but also highlighted the key-role of expertise, in both agronomy and soil biology, to help winegrowers understand and appropriate their soil quality diagnoses.

Impact of changes in pruning practices on vine growth and yield

A gradual decline in vineyards has been observed over the past twenty years worldwide. This might be explained by the climate change, practices change or the increase of dieback diseases. To increase the longevity of vines, we studied the impact of different pruning strategies in four adult and four young vineyards located in France and Spain. In France, vineyards were planted with Cabernet franc on 3309C while Spanish trials were planted with Tempranillo grafted on 110R. Vegetative expression, yield, quality of berries and wood vessels conductivity were measured. The distribution of vegetative expression, yield and berry composition between primary and secondary vegetation were quantified. Finally, tomography was used to evaluate the implication of the treatments on sap flows.
First results show that i) the respectful pruning leads to an increase of 30 to 50% more secondary shoots than the aggressive pruning in France and between 15 and 20% in Spain, ii) there is no major effect on the yield over the first two years following the implementation of the new pruning practices, although the proportion of clusters from suckers is higher on the respectful pruning method. On young vines, the development of the trunk according to a respectful pruning leads to a loss of harvest 2 years after planting. This is due to the removal, on the future trunk, of the green suckers which carrying bunches. This operation carried out in spring rather than during winter pruning, would promote a better leaf / fruit balance when the plant comes into production, and could lead to better hydraulic conduction in the vessels of the trunk. Maintaining these trials for several years will provide more robust data to assess the impact of these practices on the vines over the long term.