Résumé
Neurogenesis plays a crucial role during neurodevelopment and its dysfunction can lead to neurodevelopmental disorders. A recent hypothesis stipulates that exogenous factors could corrupt this process and predispose to neuropathological disorders later in life. The presence of pesticide residues in the diet represents a threat of which we have recently become aware of. Indeed, they could corrupt neurogenesis, especially during gestation, potentially leading to impaired neuronal and synaptic functions. We investigated the impact of fungicide residues on WT mice exposed throughout gestation. Thus, mice were exposed to fungicides, cyprodinil, mepanipyrim and pyrimethanil, alone or in cocktail. Exposure was performed through drinking water at the regulatory limit dose of the European countries (0.1 µg/L). Results showed that gestational exposure to fungicide residues substantially promoted an increase of neural precursor cells at P3. This corrupted neurogenesis was linked to increased levels of β-catenin, likely through the crosstalk of the PI3K/Akt and Wnt/β-catenin pathways, both involved in cell proliferation. Fungicide exposure also altered protein expression of PSD95 and NMDA receptors in P3 neonates, two targets of the β-catenin signaling pathway. Neurodevelopmental behavior of animals maternally exposed to the cocktail of fungicides was also explored. To conclude, corruption of neurogenesis by this chemical assault could be a fertile ground for the development of neurological diseases later in life.