Effects of glyphosate and aminomethylphosphonic acid on an isogeneic model of the human blood-brain barrier

Abstract

Glyphosate is a pesticide used for occupational and non-occupational purposes. Because glyphosate targets a metabolic pathway absent in animals, it is considered safe for humans. Yet, case reports of accidental exposure to concentrated solutions following self-inflicted poisoning documented neurological lesions suggesting a neurotoxicity. In this study, we investigated the effect of acute exposure to glyphosate (GPH) on the blood-brain barrier in vitro based on induced pluripotent stem cells (iPSCs) and compared to two chemical analogs: aminomethylphosphonic acid (AMPA) and glycine (GLY), for concentrations ranging from 0.1 μM to 1000 μM. GPH treatment (1 and 10 μM) for 24 h showed an increase BBB permeability to fluorescein, with similar outcomes for AMPA. In addition to its ability to disrupt the barrier function, GPH show evidence of permeability across the BBB. Although no detrimental effects were observed on neuron differentiation at high doses, we noted changes in neuronal cell metabolic activity and glucose uptake in brain microvascular endothelial cells (BMECs) following treatment with 100 μM GPH or AMPA. Taken together, our data indicates that accidental exposure to high level of GPH may result in neurological damage via an opening of the blood-brain barrier and an alteration of glucose metabolism.