Contribution of fungicide residue exposure to neurogenesis and corticogenesis : consequences on neurodevelopment and ageing – FunExpo

The contamination of our resources by environmental pollutants, such as pesticide residues is a major public health issue. Although brain is not often studied in classical toxicological studies, its exposure to environmental pollutants during its development could have repercussions at key moments of the individual's life. Recently, we have reported that in utero exposure to a cocktail of three anilinopyrimidine fungicides (cyprodinil, mepanipyrim and mepanipyrim) at the E.U. regulatory limit dose allowed in tap water impaired neurogenesis at 3 days post-natal (P3) in newborn mice, and altered synaptic transmission at P10.
Thus, this project aims to identify the neurotoxic properties of those fungicides and their underlying mechanisms affecting neurogenesis and thereby the correct functioning of the nervous system. Several tasks will be developed to address the objectives: (i) study the effect of anilinopyrimidines on neural stem cell fate and cortical development using the innovative multicolor fluorescent reporter strategy “MAGIC markers” combined to in utero electroporation; (ii) monitor the impact of fungicides on synaptic transmission using multi-electrode array techniques; (iii) evaluate the evolution of social interaction deficits at early stages and memory deficits between 3 and 9 months old mice; (iv) study the appearance of neurodevelopmental disorders markers, and neurodegenerative disease markers from early to late stages; and (v) identify, in neuronal cell models, the signaling pathways dysregulated by cyprodinil, mepanipyrim and pyrimethanil that would account for neurogenesis deficits, the onset of inflammatory conditions and the rise of neurodegenerative disease markers.
This project will allow us to decipher: (i) the impact of low doses of fungicides, corresponding to concentrations of contaminants found in our everyday life resources and (ii) their possible contribution to neurodevelopmental and/or neurodegenerative diseases.