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Projects / Programmes source: ARRS

Neuropsychological dysfunctions caused by low level exposure to selected environmental pollutants in susceptible population – NEURODYS

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Research activity

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 
Keywords
toxic substances, human exposure, susceptibility, neurotoxicity, exposome, internal dose, polymorphism, genes, mikrobiom, bioinformatic tools
Evaluation (rules)
source: COBISS
Citations Citations for bibliographic records in COBIB.SI that are linked to records in citation databases
source: WoS source: Scopus source: COBISS
Researchers (23)
no. Code Name and surname Research area Role Period No. of publications
1.  11130  PhD Sašo Džeroski  Engineering sciences and technologies  Researcher  2018 - 2021  1,171 
2.  19724  Vesna Fajon    Technician  2018 - 2020  296 
3.  10582  PhD Ingrid Falnoga  Medical sciences  Researcher  2018 - 2021  335 
4.  00814  PhD Ksenija Geršak  Medical sciences  Researcher  2018 - 2019  518 
5.  12315  PhD Ester Heath  Natural sciences and mathematics  Researcher  2018 - 2021  565 
6.  05027  PhD Milena Horvat  Natural sciences and mathematics  Principal Researcher  2018 - 2021  1,822 
7.  52126  PhD Marta Jagodic Hudobivnik  Natural sciences and mathematics  Researcher  2019 - 2021  121 
8.  31050  PhD Dragi Kocev  Engineering sciences and technologies  Researcher  2018 - 2021  194 
9.  25622  PhD David Kocman  Natural sciences and mathematics  Researcher  2018 - 2021  332 
10.  23041  PhD Jana Kodrič  Social sciences  Researcher  2019 - 2021  126 
11.  07673  PhD Dušan Kordiš  Natural sciences and mathematics  Researcher  2018 - 2021  214 
12.  27733  PhD Tina Kosjek  Natural sciences and mathematics  Researcher  2018 - 2021  334 
13.  39144  PhD Ana Kovačič  Natural sciences and mathematics  Junior researcher  2018 - 2021  56 
14.  00412  PhD Igor Križaj  Natural sciences and mathematics  Researcher  2018 - 2021  698 
15.  21408  PhD Aleš Lapanje  Medical sciences  Researcher  2018 - 2021  316 
16.  18287  PhD Darja Mazej  Natural sciences and mathematics  Researcher  2018 - 2021  358 
17.  09180  PhD David Neubauer  Medical sciences  Researcher  2018 - 2021  725 
18.  35473  PhD Majda Pavlin  Natural sciences and mathematics  Junior researcher  2018  117 
19.  27542  PhD Tomaž Rijavec  Medical sciences  Researcher  2018 - 2021  211 
20.  30063  PhD Janja Snoj Tratnik  Natural sciences and mathematics  Researcher  2018 - 2021  270 
21.  37818  PhD Anja Stajnko  Natural sciences and mathematics  Junior researcher  2018 - 2021  87 
22.  03950  PhD Dušan Žigon  Natural sciences and mathematics  Researcher  2018 - 2021  164 
23.  37489  PhD Igor Živković  Natural sciences and mathematics  Researcher  2018 - 2021  90 
Organisations (2)
no. Code Research organisation City Registration number No. of publications
1.  0106  Jožef Stefan Institute  Ljubljana  5051606000  85,590 
2.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  73,910 
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.
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