Neuronal development and axon growth are altered by glyphosate through a WNT non-canonical signaling pathway

COULLERY, ROMINA; FERRARI, MARÍA EDITH; ROSSO, SILVANA B

NEUROTOXICOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2016 vol. 52 p. 150 - 161

0161-813X

The growth and morphological differentiation of neurons arecritical events in the establishment of proper neuronal connectivity andfunctioning. The developing nervous system is highly susceptible todamage caused by exposure to environmental contaminants. Glyphosatecontainingherbicides are the most used agrochemicals in the world,particularly on genetically modified plants. Previous studies havedemonstrated that glyphosate induces neurotoxicity in mammals. Therefore,its action mechanism on the nervous system needs to be determined. Inthis study, we report about impaired neuronal development caused byglyphosate exposure. Particularly, we observed that the initial axonaldifferentiation and growth of cultured neurons is affected by glyphosatesince most treated cells remained undifferentiated after 1 day inculture. Although they polarized at 2 days in vitro, they elicitedshorter and unbranched axons and they also developed less complexdendritic arbors compared to controls. To go further, we attempted toidentify the cellular mechanism by which glyphosate affected neuronalmorphology. Biochemical approaches revealed that glyphosate led to adecrease in Wnt5a level, a key factor for the initial neurite developmentand maturation, as well as inducing a down-regulation of CaMKII activity.This data suggests that the morphological defects would likely be aconsequence of the decrease in both Wnt5a expression and CaMKII activityinduced by glyphosate. Additionally, these changes might be reflected ina subsequent neuronal dysfunction. Therefore, our findings highlight theimportance of establishing rigorous control on the use of glyphosatebasedherbicides in order to protect mammals´ health.