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Predictive multi-OMICS methodology for developmental neurotoxicity testing in humans early exposed to low levels of chemical contaminants

EPMA World Congress, 03-05 septembre, Bonn, Allemagne

Ardzivian, A., Ouamara, N., Boyko, N., Coumoul, X., Antignac, J.-P., Lebizec, B., Eppe, G., Renaut, J., Torsten, B., Guignard, C., Ferrante, M., Chiusano, M.L., Cuzzocrea, S., O'keeffe, G., Cryan, J., Bisson, M., Barakat, A., Hmamouchi, I., Zawia, N.

2015

The nervous system of children is especially vulnerable to chemical exposure because of a long developmental period beginning shortly after conception and continuing through adolescence. Chemical contaminants are able to interact during i) neural cell growth and differenciation, ii) synaptogenesis and iii) neuron and glial network formation, leading to permanent functional deficits and to predispose to disease later in life. Epidemiological studies suggest an increasing incidence of mental and neurological disorders among children and adults, including autism, attention-deficit hyperactivity disorder and neurodegenerative diseases such as Alzheimer disease. Environmental chemical mixtures, especially when exposures occur early in life, are suspected to contribute to the etiologies of these disorders. Developmental neurotoxicants are among the top 50 compounds listed by ATSDR. According to the European Commission, there are 143,000 registered chemicals, many which have not been evaluated for possible neurotoxic properties, let alone their effect on the developing human brain. There is a great need to find high-throughput in vitro models that can accurately screen chemicals and other contaminants for their effect on the developing human brain, both to identify, early, substances that can impair normal brain development and maturation and to identify predictive markers to create conditions that would promote prevention neurological or mental health disorders later in life and potentially induced, by early exposure to these contaminants.

However, human induced pluripotent stem cells (hiPSC) are a rational, ethical alternative model that exhibits the function and behavior of mature neurons, they are available in large quantities required for screening, and they can be established from different individuals for both disease- and genotype-specific studies.

The aim of “NeuroChemicalContam” project is to use this model in screening chemicals for developmental neurotoxic properties. The specific challenges are to identify early substances that impair normal brain development and maturation and to characterize predictive markers in order to create conditions that would promote neurological or mental health disorders later in life.

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