NEUROSOME: a multidisciplinary training network to explore the neurodevelopmental and neurological exposome

On the basis of existing epidemiological data, the effect of neurotoxic metals (mercury, methylmercury, lead, manganese, cadmium), pesticides (organophosphates, pyrethroids) and flame retardants (brominated and organophosphate) on the neuropsychological development of exposed children appears to be variable among individuals. The extent to which the observed differences could be explained by genetic vulnerability or co-exposure to more environmental chemicals is still unclear. Although environmental health literature is rich with knowledge on the potential individual steps linking environmental contamination to disease, there is a lack of established causality for developing the respective Adverse Outcome Pathways (AOPs), especially taking into account cumulative exposure, where different mechanisms of toxicity are involved, interacting between them at different levels of biological organization. Furthermore, the brain, the target organ of neurotoxicants, it is not accessible if not using highly invasive or extremely costly (e.g. neuroimaging) methods. Research is needed to identify a set of peripheral accessible markers of susceptibility, vulnerability and effects, able to predict the neuropsychological/neurological outcome. NEUROSOME is an Innovative Training Networks funded in 2017 within H2020 Marie Sklodowska-Curie Actions. The main objective of the NEUROSOME project is the development of an integrated model based on real human biomonitoring data (HBM) to identify causal associations between early environmental exposures, the human genome, and the risk of neurodevelopmental disorders and neurodegenerative diseases. In particular, the project is based on the evaluation and re-analysis of biological samples collected in existing birth cohorts (PHIME, INMA, PROBE) and in the context of a cross-Mediterranean cohort study set up specifically within NEUROSOME. The project is focused on exposure to mixtures of heavy metals and organic compounds (phthalates, plasticizers, pyrethroids, organophosphate pesticides and brominated and organophosphate flame retardants), but will also consider the role of modulation and the synergistic or additive effects of other intrinsic (such as genetic susceptibility) and extrinsic (such as diet and socio-economic status) environmental stressors. This requires the synthesis among different scientific disciplines, including environmental and exposure modelling, recent advances in toxicology (including in vitro, in vivo and in silico aspects) with a special focus on omics technologies and bioinformatics, as well as environmental epidemiology, taking stock of gene- and exposome-wide associations. The NEUROSOME objectives are pursued through an interdisciplinary network aimed at developing new knowledge and training a new generation of young European researchers on the most current issues of the relationship between the environment and health. Fifteen selected Early Stage Researchers will move between participating institutions to integrate their transdisciplinary skills and learn the different research approaches, from in silico models to human biomonitoring. A preliminary set of results collected in the first year of the project will be presented: they include collection of HBM and outcome data from the relevant population studies, transcriptomics and metabolomic signatures linked to the neurodevelopmental phenotype in biosamples, the establishment of in vitro and in vivo models of exposure to environmentally relevant chemical mixtures and generic lifetime PBBK model incorporating mixtures interaction to integrate exposure data and modelling output with HBM data.