Effects of ageing on the vulnerability of the substantia nigra pars compacta dopaminergic neurons: implications in Parkinson’s disease

The degeneration of dopaminergic neurons (DAn) in the midbrain substantia nigra pars compacta (SNpc) is a definitive feature of Parkinson's disease (PD). Although age has been established as one of the main risk factors, the role that ageing has in the development of the disease is not yet fully understood. The aim of this Thesis, therefore, was to enhance our understanding of how ageing may increase the vulnerability of SNpc DAn. To achieve this aim, isobaric tags for relative and absolute quantitation (iTRAQ) labelling combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to quantitatively compare the SNpc proteome of rats during ageing. Western blot and immunofluorescence analyses were subsequently conducted to verify some of the differentially expressed proteins from the analysis (e.g., GFAP), while immunohistochemistry analyses were performed to quantitatively and morphologically characterize the DAn of the rat SNpc themselves during ageing. From a total of 1,953 proteins that were identified and quantified in the proteomic study, the expression levels of 66 proteins were altered throughout ageing. Bioinformatic analysis revealed that proteins related to glial cells (e.g., GFAP) and the extracellular matrix (ECM) were differentially expressed in the old rat SNpc. Importantly, an unusual form of the GFAP protein (i.e., GFAPδ) was showed for the first time to be differentially expressed during ageing. In addition to this, the level of tyrosine hydroxylase (TH) expression in the SNpc throughout ageing was maintained. This was somewhat surprising as it appears that, independent of the proteomic changes, there was a general decrease in the density of rat SNpc DAn together with an increase of their soma size with ageing, which might indicate that the remaining DAn are able to maintain the level of tyrosine hydroxylase (TH) expression in the SNpc throughout ageing. These results were followed by an in vitro investigation of the role astrocytes play in the vulnerability of DAn. To do this, primary cultures of embryonic DAn were challenged with the toxin 6-hydroxidopamine (6-OHDA) after reducing the number of astrocytes in the cultures in a unique way (i.e., by using the anti-mitotic drug paclitaxel). Though the anti-mitotic drug was successful in reducing astrocytes in the cultures, it was difficult to test the effect this had on combating the effects of 6-OHDA on DAn because the toxin also affected the viability of the remaining astrocytes in culture. Lastly, multiple multi-study proteomic comparisons of published studies on the ageing nervous system and PD demonstrated that metabolism, oxidation-reduction mechanisms, mitochondrial function and immune system were biological processes and pathways enriched in both ageing and PD. Because some of these biological processes were the same as those found differentially expressed in the proteomics study of ageing conducted here, this support the idea that they may be key toward understanding how ageing is involved in the development of PD. In conclusion, this Thesis showed that ageing alters the metabolic support associated with mitochondrial and oxidation-reduction functions (as it happens in PD) and suggests that this might have considerable repercussions on highly reactive oxygen species (ROS) sensitive neurons such as SNpc DAn. Adding to this, the alteration of proteins related to glial cells (e.g., astrocytes) might affect their protective function in the SNpc during a time when they are become even more essential to the survival of DAn

Endobolome, a New Concept for Determining the Influence of Microbiota Disrupting Chemicals (MDC) in Relation to Specific Endocrine Pathogenesis

This work was carried out within the frame of GP/EFSA/ENCO/380 2018/03/G04: OBEMIRISK: Knowledge platform for assessing the risk of Bisphenols on gut microbiota and its role in obesogenic phenotype: looking for biomarkers. This research was also funded by Spanish State Research Agency (SRA) EIN2019-103431, EIN2019-103082 and Proyecto cofinanciado FEDER-Consejeria de Salud y Familias, Junta de Andalucia PE-0250-2019.The results presented in this article constitute part of YG-O doctoral thesis, performed in the Nutrition and Food Sciences Doctorate Program of the University of Granada.Endogenous steroid hormones and Endocrine Disrupting Chemicals (EDC) interact with gut microbiota through different pathways. We suggest the use of the term “endobolome” when referring to the group of gut microbiota genes and pathways involved in the metabolism of steroid hormones and EDC. States of dysbiosis and reduced diversity of the gut microbiota may impact and modify the endobolome resulting at long-term in the development of certain pathophysiological conditions. The endobolome might play a central role in the gut microbiota as seen by the amount of potentially endobolome-mediated diseases and thereby it can be considered an useful diagnostic tool and therapeutic target for future functional research strategies that envisage the use of next generation of probiotics. In addition, we propose that EDC and other xenobiotics that alter the gut microbial composition and its metabolic capacities should be categorized into a subgroup termed “microbiota disrupting chemicals” (MDC). This will help to distinguish the role of contaminants from other microbiota natural modifiers such as those contained or released from diet, environment, physical activity and stress. These MDC might have the ability to promote specific changes in the microbiota that can ultimately result in common intestinal and chronic or long-term systemic diseases in the host. The risk of developing certain disorders associated with gut microbiota changes should be established by determining both the effects of the MDC on gut microbiota and the impact of microbiota changes on chemicals metabolism and host susceptibility. In any case, further animal controlled experiments, clinical trials and large epidemiological studies are required in order to establish the concatenated impact of the MDC-microbiota-host health axis.OBEMIRISK: Knowledge platform for assessing the risk of Bisphenols on gut microbiota and its role in obesogenic phenotype: looking for biomarkers GP/EFSA/ENCO/380 2018/03/G04Spanish State Research Agency (SRA) EIN2019-103431 EIN2019-103082Junta de Andalucia PE-0250-201

Quantitative proteomic profiling of the rat substantia nigra places glial fibrillary acidic protein at the hub of proteins dysregulated during aging : implications for idiopathic Parkinson’s disease

This work was made possible by generous funding from the Keele University ACORN scheme and Keele University School of Medicine.There is a strong correlation between aging and onset of idiopathic Parkinson's disease, but little is known about whether cellular changes occur during normal aging that may explain this association. Here, proteomic and bioinformatic analysis was conducted on the substantia nigra (SN) of rats at four stages of life to identify and quantify protein changes throughout aging. This analysis revealed that proteins associated with cell adhesion, protein aggregation and oxidation‐reduction are dysregulated as early as middle age in rats. Glial fibrillary acidic protein (GFAP) was identified as a network hub connecting the greatest number of proteins altered during aging. Furthermore, the isoform of GFAP expressed in the SN varied throughout life. However, the expression levels of the rate‐limiting enzyme for dopamine production, tyrosine hydroxylase (TH), were maintained even in the oldest animals, despite a reduction in the number of dopamine neurons in the SN pars compact(SNc) as aging progressed. This age‐related increase in TH expression per neuron would likely to increase the vulnerability of neurons, since increased dopamine production would be an additional source of oxidative stress. This, in turn, would place a high demand on support systems from local astrocytes, which themselves show protein changes that could affect their functionality. Taken together, this study highlights key processes that are altered with age in the rat SN, each of which converges upon GFAP. These findings offer insight into the relationship between aging and increased challenges to neuronal viability, and indicate an important role for glial cells in the aging process.Publisher PDFPeer reviewe

Presence of Parabens and Bisphenols in Food Commonly Consumed in Spain

Given the widespread use of bisphenols and parabens in consumer products, the assessment of their intake is crucial and represents the first step towards the assessment of the potential risks that these compounds may pose to human health. In the present study, a total of 98 samples of food items commonly consumed by the Spanish population were collected from different national supermarkets and grocery stores for the determination of parabens and bisphenols. Our analysis demonstrated that 56 of the 98 food samples contained detectable levels of parabens with limits of quantification (LOQ) between 0.4 and 0.9 ng g-1. The total concentration of parabens (sum of four parabens: åparabens) ranged from below the LOQ to 281.7 ng g-1, with a mean value of 73.86 ng g-1. A total of 52% of the samples showed detectable concentrations of bisphenols. Bisphenol A (BPA) was the most frequently detected bisphenol in the food samples analysed, followed by bisphenol S (BPS) and bisphenol E (BPE). Bisphenol AF (BPAF), bisphenol B (BPB) and bisphenol P (BPP) were not found in any of the analysed samples. LOQ for these bisphenols were between 0.4 and 4.0 ng g-1

Bisphenol A Analogues in Food and Their Hormonal and Obesogenic Effects: A Review

Bisphenol A (BPA) is the most well-known compound from the bisphenol family. As BPA has recently come under pressure, it is being replaced by compounds very similar in structure, but data on the occurrence of these BPA analogues in food and human matrices are limited. The main objective of this work was to investigate human exposure to BPA and analogues and the associated health effects. We performed a literature review of the available research made in humans, in in vivo and in vitro tests. The findings support the idea that exposure to BPA analogues may have an impact on human health, especially in terms of obesity and other adverse health effects in children.This research was funded by Plan Estatal de I+D+I 2013-2016 Proyecto cofinanciado FEDER-ISCIII PI17/01758 and by Fundación Mapfre MAPFRE2018

Factors Associated with Exposure to Dietary Bisphenols in Adolescents

Obesogenic endocrine-disrupting chemicals, such as bisphenol A (BPA) and its analogue bisphenol S (BPS), seem to play an important role in the development of obesity, although contradictory results have been reported. The aim of the present study was to conduct a gender analysis of the factors associated with exposure to dietary bisphenols in 585 Spanish adolescents. Dietary BPA and BPS exposure was assessed using a food frequency questionnaire. Foods and macronutrients accounting for more than 95% of energy intake were selected for analysis. Stepwise regression was used to estimate the foods that most contributed to dietary bisphenol exposure in the sample. Gender-related factors associated with greater dietary bisphenol exposure were evaluated using multivariate logistic regression models. Canned tuna was the main dietary source of BPA and BPS in both adolescent boys and girls. Overweight/obese girls showed a higher risk of high dietary exposure to BPA (odds ratio (OR): 3.38, 95% confidence interval (CI): 1.25–9.07) and total bisphenols (OR: 2.81, 95% CI: 1.03–7.67) in comparison with girls with a BMI lower than 25 kg/m2 . Present results indicate a positive association of dietary exposure to both total bisphenols and BPA with being overweight/obese in adolescent girls.GP/EFSA/ENCO/380 2018/03/G04: OBEMIRISK: Knowledge platform for assessing the risk of bisphenol on gut microbiota and its role in obesogenic phenotypes: looking for biomarkers’ frameworkPlan Estatal de I + D + I 2013–2016FEDER-ISCIII PI17/01758FEDER-Consejería de Salud y FamiliasJunta de Andalucía PE-0250–2019FEDER-Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y Universidades/ Proyecto P18-RT-4247Fundación Mapfre MAPFRE201

Dietary exposure to parabens and body mass index in an adolescent Spanish population

This work was carried out in line with 'GP/EFSA/ENCO/380 2018/03/G04: OBEMIRISK: Knowledge platform for assessing the risk of Bisphenols on gut microbiota and its role in obesogenic phenotype: looking for biomarkers'. This research was also funded by Plan Estatal de I + D + I 2013-2016 and co-funded by FEDER-ISCIII PI17/01758, FEDER-Consejeria de Salud y Familias, Junta de Andalucia PE-0250-2019, FEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades/Proyecto P18-RT-4247. All individuals participating in this research signed an informed consent form and the study protocol was approved by the Ethics Com-mittee of the University of Granada.Parabens are alkyl esters of p-hydroxybenzoic acid which are extensively used in cosmetics, pharmaceuticals and foodstuffs due to their antimicrobial properties. The most commonly used parabens are methyl-(MeP), ethyl- (EtP), propyl-(PrP) and butyl-(BuP) paraben. Most human exposure to parabens is achieved through the consumption of food or pharmaceutical products and the use of personal care products. However, studies on dietary parabens exposure and the associated factors are very scarce. The main aim of the present study was to explore factors associated with dietary exposure to parabens in Spanish adolescents according to gender. Dietary data and anthropometric measures were collected from 585 adolescents (53.4% boys) aged 12–16 years. Parabens exposure through diet was assessed using a food frequency questionnaire with food products providing more than 95% of energy and macronutrient intake being included in analysis. Stepwise regression was used to identify the foods that most contributed to parabens intake. Logistic regression was used to evaluate factors predicting higher dietary exposure to parabens. The main contributors to dietary MeP, EtP, PrP and BuP exposure in adolescent boys were eggs (41.9%), canned tuna (46.4%), bakery and baked goods products (57.3%) and pineapple (61.1%). In adolescent girls, the main contributors were apples and pears (35.3%), canned tuna (42.1%), bakery and baked goods products (55.1%) and olives (62.1%). Overweight/obese girls were more likely to belong to the highest tertile of overall parabens intake (odds ratio [OR]: 3.32; 95% confidence interval [95% CI]: 1.21–9.15) and MeP (OR: 3.05; 95% CI: 1.14–8.12) than those with a body mass index lower than 25 kg/m2. These findings suggest a positive association between dietary exposure to parabens and overweight/obesity in adolescent girls.Plan Estatal de I + D + I 2013-2016FEDER-ISCIII PI17/01758FEDER-Consejeria de Salud y FamiliasJunta de Andalucia PE-0250-2019FEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades/Proyecto P18-RT-424

Levels of Bisphenol A and its analogs in nails, saliva, and urine of children: a case control study

Introduction: A growing number of studies link the increase in overweight/ obesity worldwide to exposure to certain environmental chemical pollutants that display obesogenic activity (obesogens). Since exposure to obesogens during the first stages of life has been shown to have a more intense and pronounced effect at lower doses, it is imperative to study their possible effects in childhood. The objective here was to study the association of Bisphenol A (BPA) and 11 BPA analogs in children, using three biological matrices (nails, saliva and urine), and overweight and obesity (n = 160). Methods: In this case–control study, 59 overweight/obese children and 101 controls were included. The measuring of Bisphenols in the matrices was carried out by ultra-high performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC-MS/MS). Logistic regression was used to study the association between overweight/obesity and Bisphenol exposure. Results: The results suggested that BPF in nails is associated with overweight/ obesity in children (OR:4.87; p = 0.020). In saliva, however, the highest detected concentrations of BPAF presented an inverse association (OR: 0.06; p = 0.010) with overweight/obesity. No associations of statistical significance were detected between exposure to BPA or its other analogs and overweight/obesity in any of the biological matrices.FEDER-Consejería de Salud y Familias’ of the Junta de Andalucía PE-0250-201

Changes in fatty acid dietary profile affect the brain–gut axis functions of healthy young adult rats in a sex-dependent manner

This article belongs to the Special Issue Dietary Management of Gastrointestinal Diseases and Disorders.Dietary modifications, including those affecting dietary fat and its fatty acid (FA) composition, may be involved in the development of brain–gut axis disorders, with different manifestations in males and females. Our aim was to evaluate the impact of three purified diets with different FA composition on the brain–gut axis in rats of both sexes. Male and female Wistar rats fed a cereal-based standard diet from weaning were used. At young adult age (2–3 months old), animals were divided into three groups and treated each with a different refined diet for 6 weeks: a control group fed on AIN-93G diet containing 7% soy oil (SOY), and two groups fed on AIN-93G modified diets with 3.5% soy oil replaced by 3.5% coconut oil (COCO) or 3.5% evening primrose oil (EP). Different brain–gut axis parameters were evaluated during 4–6 weeks of dietary intervention. Compared with SOY diet (14% saturated FAs, and 58% polyunsaturated FAs), COCO diet (52.2% saturated FAs and 30% polyunsaturated FAs) produced no changes in brain functions and minor gastrointestinal modifications, whereas EP diet (11.1% saturated FAs and 70.56% polyunsaturated FAs) tended to decrease self-care behavior and colonic propulsion in males, and significantly increased exploratory behavior, accelerated gastrointestinal transit, and decreased cecum and fecal pellet density in females. Changes in FA composition, particularly an increase in ω-6 polyunsaturated FAs, seem to facilitate the development of brain–gut axis alterations in a sex-dependent manner, with a relatively higher risk in females.We thank Comunidad Autónoma de Madrid for the technician contract of Lorena Blanco (PEJ15/BIO/TL-0580) and the predoctoral contract of Yolanda López-Tofiño (PEJD-2017-PRE/BMD-3924), and URJC for the predoctoral contracts of Yolanda López-Tofiño and Carlos Gálvez-Robleño (both under PREDOC20-054 call). Damian Jacenik was a recipient of fellowship funded by Faculty of Biology and Environmental Protection, University of Lodz, Poland.Peer reviewe

Identidad Onubense: Opinión y prácticas sociales respecto a urbanismo, patrimonio y entorno

Presentation of the research results on the Huelva [Onubense] Identity, 2020-2021. The results were presented at the Conference on Knowledge Transfer held on November 25, 2021 (University of Huelva, ETSI). It corresponds to the project: Huelva Identity: Opinion and social practices regarding urban planning, heritage, and environment. See more information at: https://eseis.es/investigacion/identidad-onubensePresentation of the research results on the Huelva [Onubense] Identity, 2020-2021. The results were presented at the Conference on Knowledge Transfer held on November 25, 2021 (University of Huelva, ETSI). It corresponds to the project: Huelva Identity: Opinion and social practices regarding urban planning, heritage, and environment. See more information at: https://eseis.es/investigacion/identidad-onubenseCátedra de la Provincia, UHU - Diputación de Huelva. Facultad de Trabajo Social. Autoridad Portuaria de Huelva. Consejo Social, UHU. Grupo de investigación Estudios Sociales E Intervención Social (Grupo ESEIS). Centro de Pensamiento Contemporáneo e Innovación para el Desarrollo Social (COIDESO