Modeling and monitoring the effects on the central nervous system of a chronic exposure to low dose of pollutants: an innovative strategy with first results - Université de Lorraine Access content directly
Poster Communications Year : 2018

Modeling and monitoring the effects on the central nervous system of a chronic exposure to low dose of pollutants: an innovative strategy with first results

Nguyen Tran
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Abstract

Chronic low dose exposure and possible cumulative effects of various pollutants could affect consumer health and may contribute to the development of neurodegenerative pathologies. Due to the highly complex and long exposure, a clear link between diet contaminants and neurodegenerative diseases has often been suspected, but rarely proven. An additional drawback is the high diversity of in vitro models (cancer cell lines, stem cells, primary embryonic cells), bringing additional complexity in the deciphering of the observed effects of pollutants. To properly assess the risks and to reevaluate the maximal acceptable dose of specific pollutants in the food chain, there is a need for efficient modeling of pollutant effects on the central nervous system (CNS). To address this need, we are developing a new approach to evaluate the consequences on neuronal health of long time exposure to pollutants. We are actually re-evaluating the neurotoxic effects of chlordecone (CLD) as proof-of-concept of our strategy. Several concentrations of CLD were used to treat a variety of mouse primary neurons isolated from different postnatal CNS areas. We then assessed neuronal functions using specific markers for neuronal death, neurite development and synapse formation. In parallel, we produced cerebrospinal fluid (CSF) from pigs exposed to CLD via contaminated food. This CSF containing CLD and its by-products that are able to cross the blood brain barrier could then be used on the same cultures to compare its effect with that obtained following direct treatment with the molecule. We were able to identify a direct neurotoxic effect (10 µM) on specific purified neuronal cultures together with more subtle damages at lower concentrations including neurite arborization defects (0.1 to 1µM depending on the respective neuronal cultures). Additional effects on pure glia cell cultures at higher concentrations (100 µM) suggest a reactive gliosis in the whole animal. These observations were confirmed by CSF treatment using CLD-contaminated CSF but not with CSF from control pigs. In addition, the dose with no observable effects is at least 10 times lower using primary postnatal neuronal cultures compared to embryonic cultures. Our experimental model is therefore much more sensitive and may reflect more precisely the consequences of chronic CLD exposure. Our strategy could help to re-evaluate the CNS effects of this remnant pollutant present in West Indies soils.
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hal-03957693 , version 1 (26-01-2023)

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  • HAL Id : hal-03957693 , version 1

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Thomas Claudepierre, Frédéric Desor, Céline Cakir-Kiefer, Matthieu Delannoy, Aseel El Hajj, et al.. Modeling and monitoring the effects on the central nervous system of a chronic exposure to low dose of pollutants: an innovative strategy with first results. SETAC Europe 28th Annual Meeting, May 2018, Rome, Italy. SETAC Europe 28th Annual Meeting Abstract Book, pp.221, 2018. ⟨hal-03957693⟩
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