Understanding the effects of air pollution on neurogenesis and gliogenesis in the growing and adult brain

Exposure to air pollution - and particularly to particulate matter (PM) - is strongly associated with higher risk of neurodevelopmental disorders, poor mental health and cognitive defects. In animal models, disruption of CNS development and disturbances of adult neurogenesis contribute to PM neurotoxicity. Recent studies show that gestational PM exposure not only affects embryonic neurodevelopment, but also disturbs postnatal brain growth and maturation, by interfering with neurogenic/gliogenic events, myelination and synaptogenesis. Similarly, adult neurogenesis is affected at many levels, from neural stem cell amplification up to the maturation and integration of novel neurons in the adult brain parenchyma. The underlying mechanisms are still by and large unknown. Beyond microglia activation and neuroinflammation, recent studies propose a role for novel epigenetic mechanisms, including DNA methylation and extracellular vesicles-associated microRNAs

Particulate matter exposure shapes DNA methylation through the lifespan

Exposure to airborne particulate matter (PM) has been associated with detrimental health effects. DNA methylation represents the most well-studied epigenetic factor among the possible mechanisms underlying this association. Interestingly, changes of DNA methylation in response to environmental stimuli are being considered for their role in the pathogenic mechanism, but also as mediators of the body adaptation to air pollutants. Several studies have evaluated both global and gene-specific methylation in relation to PM exposure in different clinical conditions and life stages. The purpose of the present literature review is to evaluate the most relevant and recent studies in the field in order to analyze the available evidences on long- and short-term PM exposure and DNA methylation changes, with a particular focus on the different life stages when the alteration occurs. PM exposure modulates DNA methylation affecting several biological mechanisms with marked effects on health, especially during susceptible life stages such as pregnancy, childhood, and the older age. Although many cross-sectional investigations have been conducted so far, only a limited number of prospective studies have explored the potential role of DNA methylation. Future studies are needed in order to evaluate whether these changes might be reverted

Molecular and epigenetic markers as promising tools to quantify the effect of occupational exposures and the risk of developing non-communicable diseases

Non-communicable diseases (NCDs) are chronic diseases that are by far the leading cause of death in the world. Many occupational hazards, together with social, economic and demographic factors, have been associated to NCDs development. Genetic susceptibility or environmental exposures alone are not usually sufficient to explain the pathogenesis of NCDs, but can be integrated in a more complex scenario that can result in pathological phenotypes. Epigenetics is a crucial component of this scenario, as its changes are related to specific exposures, therefore potentially able to display the effects of environment on the genome, filling the gap between genetic asset and environment in explaining disease development. To date, the most promising biomarkers have been assessed in occupational cohorts as well as in case/control studies and include DNA methylation, histone modifications, microRNA expression, extracellular vesicles, telomere length, and mitochondrial alterations

Fieldtrips and Virtual Tours as Geotourism Resources: Examples from the Sesia Val Grande UNESCO Global Geopark (NW Italy)

In the 20th anniversary year of the European Geopark Network, and 5 years on from the receipt of the UNESCO label for the geoparks, this research focuses on geotourism contents and solutions within one of the most recently designated geoparks, admitted for membership in 2013: the Sesia Val Grande UNESCO Global Geopark (Western Italian Alps). The main aim of this paper is to corroborate the use of fieldtrips and virtual tours as resources for geotourism. The analysis is developed according to: i) geodiversity and geoheritage of the geopark territory; ii) different approaches for planning fieldtrip and virtual tours. The lists of 18 geotrails, 68 geosites and 13 off-site geoheritage elements (e.g., museums, geolabs) are provided. Then, seven trails were selected as a mirror of the geodiversity and as container of on-site and off-site geoheritage within the geopark. They were described to highlight the different approaches that were implemented for their valorization. Most of the geotrails are equipped with panels, and supported by the presence of thematic laboratories or sections in museums. A multidisciplinary approach (e.g., history, ecology) is applied to some geotrails, and a few of them are translated into virtual tours. The variety of geosciences contents of the geopark territory is hence viewed as richness, in term of high geodiversity, but also in term of diversification for its valorization

Epigenetics and lifestyle

The concept of 'lifestyle' includes different factors such as nutrition, behavior, stress, physical activity, working habits, smoking and alcohol consumption. Increasing evidence shows that environmental and lifestyle factors may influence epigenetic mechanisms, such as DNA methylation, histone acetylation and miRNA expression. It has been identified that several lifestyle factors such as diet, obesity, physical activity, tobacco smoking, alcohol consumption, environmental pollutants, psychological stress and working on night shifts might modify epigenetic patterns. Most of the studies conducted so far have been centered on DNA methylation, whereas only a few investigations have studied lifestyle factors in relation to histone modifications and miRNAs. This article reviews current evidence indicating that lifestyle factors might affect human health via epigenetic mechanisms

Out-of-hospital cardiac arrests in a large metropolitan area : synergistic effect of exposure to air particulates and high temperature

Aims: Air pollution and climate change are intrinsically linked to emerging hazards for global health. High air particulate matter (PM) levels may trigger out-of-hospital cardiac arrest (OHCA). High temperature could act synergistically with PM in determining OHCA. The aim of the present study was to investigate the effect of PM exposure alone, and in combination with temperature, on the risk of OHCA, in a large European metropolitan area with population >4 million. Methods: We evaluated the association between short-term PM exposure, temperature, and the risk of OHCA over a two-year study period, allowing us to investigate 5761 events using a time-stratified case-crossover design combined with a distributed lag non-linear model. Results: Higher risk of OHCA was associated with short-term exposure to PM10. The strongest association was experienced three days before the cardiac event where the estimated change in risk was 1.70% (0.48\u20132.93%) per 10 \ub5g/m3 of PM. The cumulative exposure risk over the lags 0\u20136 was 8.5% (0.0\u201317.9%). We observed a joint effect of PM and temperature in triggering cardiac arrests, with a maximum effect of 14.9% (10.0\u201320.0%) increase, for high levels of PM before the cardiac event, in the presence of high temperature. Conclusion: The present study helps to clarify the controversial role of PM as OHCA determinant. It also highlights the role of increased temperature as a key factor in triggering cardiac events. This evidence suggests that tackling both air pollution and climate change might have a relevant impact in terms of public health

Particulate Air Pollution, Clock Gene Methylation, and Stroke : Effects on Stroke Severity and Disability

Circadian rhythm disturbances have been consistently associated with the development of several diseases, particularly cardiovascular diseases (CVDs). A central clock in the brain maintains the daily rhythm in accordance with the external environment. At the molecular level, the clock is maintained by \u201cclock genes\u201d, the regulation of which is mainly due to DNA methylation, a molecular mechanism of gene expression regulation, able to react to and be reprogrammed by environmental exposure such as exposure to particulate matter (PM). In 55 patients with a diagnosis of acute ischemic stroke, we showed that PM2.5 exposure experienced before the event influenced clock genes methylation (i.e., circadian locomotor output cycles protein kaput CLOCK, period 2 PER2, cryprochrome 1 CRY1, Neuronal PAS Domain Protein 2 NPAS2), possibly modulating the patient prognosis after the event, as cryptochrome 1 CRY1 and period 1 PER1 methylation levels were associated with the Rankin score. Moreover, if PM2.5 annual average was low, CRY1/CRY2 methylation levels were positively associated with the National Institutes of Health Stroke Scale (NIHSS) score, whereas they were negatively associated if PM2.5 exposure was high. Whether epigenetic changes in clock genes need to be considered as a prognostic marker of stroke or rather a causal agent in stroke development remains to be determined. Further studies are needed to determine the role of clock gene methylation in regulating the response to and recovery after a stroke event

Effects of particulate matter on genomic DNA methylation content and iNOS promoter methylation

Background: Altered patterns of gene expression mediate the effects of particulate matter (PM) on human health, but mechanisms through which PM modifies gene expression are largely undetermined. Objectives: We aimed at identifying short- and long-term effects of PM exposure on DNA methylation, a major genomic mechanism of gene expression control, in workers in an electric furnace steel plant with well-characterized exposure to PM with aerodynamic diameters < 10 μm (PM10). Methods: We measured global genomic DNA methylation content estimated in Alu and long interspersed nuclear element-1 (LINE-1) repeated elements, and promoter DNA methylation of iNOS (inducible nitric oxide synthase), a gene suppressed by DNA methylation and induced by PM exposure in blood leukocytes. Quantitative DNA methylation analysis was performed through bisulfite PCR pyrosequencing on blood DNA obtained from 63 workers on the first day of a work week (baseline, after 2 days off work) and after 3 days of work (postexposure). Individual PM10 exposure was between 73.4 and 1,220 μg/m3. Results: Global methylation content estimated in Alu and LINE-1 repeated elements did not show changes in postexposure measures compared with baseline. PM10 exposure levels were negatively associated with methylation in both Alu [β = –0.19 %5-methylcytosine (%5mC); p = 0.04] and LINE-1 [β = –0.34 %5mC; p = 0.04], likely reflecting long-term PM10 effects. iNOS promoter DNA methylation was significantly lower in postexposure blood samples compared with baseline (difference = –0.61 %5mC; p = 0.02). Conclusions: We observed changes in global and gene specific methylation that should be further characterized in future investigations on the effects of PM