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

COULLERY, ROMINA; ROSSO SILVANA

Mar del Plaa

Congreso; XXX Congreso Anual de la SAN; 2015

Sociedad Argentina de Investigación en Neurociencia.

The growth and morphological differentiation of neurons are critical events in the establishment of proper neuronal connectivity and neural function. Developing nervous system is highly susceptible to damage caused by exposure to environmental contaminants. Although Glyphosate-containing herbicides are some of the most used agrochemicals in the world, toxic effects have been reported in mammals. However, its action mechanism on the nervous system remains unclear. Here, we report the impaired neuronal development induced by glyphosate exposure. We observed that the initial axonal differentiation and growth on cultured neurons is affected since after 1 day most glyphosate treated cells remained undifferentiated. Although, they polarized at 2 days in vitro, they developed shorter and unbranched axons and also less complex dendritic arbors compared to controls. To go further, we attempted to identify the cellular mechanism by which glyphosate affected neuronal morphology. Biochemical approaches revealed that glyphosate led to a decrease in Wnt5a, a key factor for the initial neurite development and maturation, as well as a down-regulation of CaMKII. These data suggest that the morphological defects induced by glyphosate could probably be a consequence of a decrease in both Wnt5a expression and CaMKII activity that would likely be reflected in a neuronal dysfunction; therefore it highlights the importance of establishing rigorous control on the use of glyphosate-based herbicides.