Projects / Programmes
Neuropsychological dysfunctions caused by low level exposure to selected environmental pollutants in susceptible population – NEURODYS
| Code |
Science |
Field |
Subfield |
| 1.08.00 |
Natural sciences and mathematics |
Control and care of the environment |
|
| Code |
Science |
Field |
| B700 |
Biomedical sciences |
Environmental health |
| Code |
Science |
Field |
| 1.05 |
Natural Sciences |
Earth and related Environmental sciences |
toxic substances, human exposure, susceptibility, neurotoxicity, exposome, internal dose, polymorphism, genes, mikrobiom, bioinformatic tools
Researchers (23)
Organisations (2)
Abstract
Environmental pollutants, including selected toxic elements and their species and organic compounds, are among the known causes for neurodevelopmental diseases, the prevalence of which seem to be increasing world-wide. Sub-clinical decrements in neuro-psychological functions are even more common than neurodevelopmental disorders and can play an important role in aetiology of neurological disorders later in life. Response depends strongly on the individual's compensation mechanisms, particularly at low, environmentally relevant exposures, and may include (epi)genetic predisposition and/or human microbiome. A notable increase of intensity of studies related to the variability in susceptibility to neurotoxic effects at low low-level of exposure to environmental toxicants has been evidenced.
The present proposal builds on the existing cohort of children PHIME (Public Health Impact of long-term, low-level mixed element exposure in susceptible population strata to toxic metals, 2000-2006) in which child neurodevelopment in relation to mercury (Hg) exposure among residents in the Mediterranean coastal regions of Italy, Slovenia, Croatia and Greece was assessed. The results of the neurodevelopment performance at the 18 months have shown that higher fish consumption during pregnancy was associated with cognitive and language (but not motor) neurodevelopment performance.The subset of children from this cohort were further assessed at 6 to 8 years of age in three countries Slovenia, Croatia and Italy as part of the Life+CHROME project. As a rational approach, this proposal aims to further exploit the available data and fill data gaps by additional chemical, biochemical and molecular analysis. The main goal of the present proposal is to establish associations between environmental exposure, human (epi)genome and neuropsychological performance, taking into account for the first time also the role of microbiome. As the birth cohorts in three countries followed exactly the same study protocol, the formation of unified study cohort is justified and allows for the sufficient stitistical power in data analyses and interpretation. Moreover, this proposal is timely as it coincides with the recruitment of a new cohort in Ljubljana and Rijeka regions as part of the EU EXHES/HEALS project. This will allow further validation of the study outcomes using methodology built on the validated approach and data.
Strong and committed interdisciplinary institutional arrangements is composed of partners in Slovenia (Jožef Stefan Institute, University Clinical Center Ljubljana) with the expertise covering chemical and biochemical analytical work, pharmacokinetic modelling, experience in recruitment and neurodevelopment testing, bioinformatics and most advanced machine learning techniques ultimately needed for data interpretation and exploitation. The international partners will contribute the data needed for inclusion of Croatian and Italian cohort (University Medical center in Rijeka and Burlo Garofolo. Trieste) as well as classical biostatistical tools. The contribution from Swedish partners, namely Karolinska Institute, Stockholm and Chalmers University, will contribute expertise in advanced genotyping and epigenetic analysis and microbiome, respectively.
Finally, the project will disseminate the results to the science community through an ambitios publication plan, while strong engagement of early stage researchers will create opportunities for their enhanced career prospects in this perspective interdisciplinary science domain. Communication of the study results to different health and environmental sectors at national and international level will also improve the understanding and the use of the complex gene-environment interactions in chemical management actions. The empowerment of citizens through their active participation (recruited subjects) as well outreach activities will also be an integral part of the project implementation plan
Significance for science
The results will give new important information on mechanisms of neurotoxic effects caused by environmental pollutants and confounding factors that will broaden and deepen our understanding of the associated mechanisms on the molecular, and organism levels. This will be achieved through the development of an integrative exposure biology-based framework starting from Human Biomonitoring (HBM) data for identifying the causal associations among the human genome, environmental exposure and neurodevelopmental diseases. This would rely on the evaluation and reanalysis of existing cohort biosamples (e.g. PHIME, CROME, and HEALS) and selected re-sampling and external exposome assessment of the populations involved in the above studies. From these studies, it was found that the effect of toxic compounds was variable among individuals, even if the exposure levels were similar. The extent to which the differences observed might be explained by genetics, sociodemographic factors or by co-exposures to multiple environmental chemicals remains unclear. The proposed study addresses these issues and compliment them with the human microbiome for which it is known to affect several processes in the human body.
The study will address the inter-individual differences in genetic, epigenetic or microbiome based susceptibility in relation to chemical’s exposure – this represent a significant advancement in the study approaches and will contribute to studies that try to resolve inconsistencies at low level of exposure in susceptible population groups, therefore providing improved understanding of the effects of genetic and signalling pathways that modulate detrimental effects of toxic metals and selected organic compounds at low exposure.
In particular this study will contribute to the new science based evidence needed in WHO guidelines and UNEP Minamata Convention on mercury adopted in 2013. The Article 16 of this Convention on health aspects calls for “the development and implementation of strategies and programs to identify and protect populations at risk, particularly vulnerable populations, and which may include adopting science-based health guidelines relating to the exposure to mercury and mercury compounds, setting targets for mercury exposure reduction, ..... .” Moreover, the project will contribute to the EU commitment to the Parma Declaration 2010, as well as the Rio+20 agenda and the new UN Sustainable Development Goals (SDGs) and the new EU HBM initiative (HBM4EU) through.
Through publications in international journals and other dissemination and communication activities, we will contribute to increasing the visibility of our researchers and Slovenia in the international arena. It is not negligible that the project will involves several young researchers, and will be transferred to higher education mainly at postgraduate level.
Significance for the country
The results will give new important information on mechanisms of neurotoxic effects caused by environmental pollutants and confounding factors that will broaden and deepen our understanding of the associated mechanisms on the molecular, and organism levels. This will be achieved through the development of an integrative exposure biology-based framework starting from Human Biomonitoring (HBM) data for identifying the causal associations among the human genome, environmental exposure and neurodevelopmental diseases. This would rely on the evaluation and reanalysis of existing cohort biosamples (e.g. PHIME, CROME, and HEALS) and selected re-sampling and external exposome assessment of the populations involved in the above studies. From these studies, it was found that the effect of toxic compounds was variable among individuals, even if the exposure levels were similar. The extent to which the differences observed might be explained by genetics, sociodemographic factors or by co-exposures to multiple environmental chemicals remains unclear. The proposed study addresses these issues and compliment them with the human microbiome for which it is known to affect several processes in the human body.
The study will address the inter-individual differences in genetic, epigenetic or microbiome based susceptibility in relation to chemical’s exposure – this represent a significant advancement in the study approaches and will contribute to studies that try to resolve inconsistencies at low level of exposure in susceptible population groups, therefore providing improved understanding of the effects of genetic and signalling pathways that modulate detrimental effects of toxic metals and selected organic compounds at low exposure.
In particular this study will contribute to the new science based evidence needed in WHO guidelines and UNEP Minamata Convention on mercury adopted in 2013. The Article 16 of this Convention on health aspects calls for “the development and implementation of strategies and programs to identify and protect populations at risk, particularly vulnerable populations, and which may include adopting science-based health guidelines relating to the exposure to mercury and mercury compounds, setting targets for mercury exposure reduction, ..... .” Moreover, the project will contribute to the EU commitment to the Parma Declaration 2010, as well as the Rio+20 agenda and the new UN Sustainable Development Goals (SDGs) and the new EU HBM initiative (HBM4EU) through.
Through publications in international journals and other dissemination and communication activities, we will contribute to increasing the visibility of our researchers and Slovenia in the international arena. It is not negligible that the project will involves several young researchers, and will be transferred to higher education mainly at postgraduate level.
Most important scientific results
Interim report
Most important socioeconomically and culturally relevant results
Interim report
