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Multiple effects of the herbicide glufosinate-ammonium and its main metabolite on neural stem cells from the subventricular zone of newborn mice

By Justyne Feat-Vetel, Vanessa Larrigaldie, Géraldine Meyer-Dilhet, Ameziane Herzine, Camille Mougin, Anthony Laugeray, Thierry Gefflaut, Olivier Richard, Valerie Quesniaux, Céline Montécot-Dubourg and Stéphane Mortaud

Abstract

International audienceThe globally used herbicide glufosinate-ammonium (GLA) is structurally analogous to the excitatory neurotransmitter glutamate, and is known to interfere with cellular mechanisms involved in the glutamatergic system. In this report, we used an in vitro model of murine primary neural stem cell culture to investigate the neurotoxicity of GLA and its main metabolite, 4-methylphosphinico-2-oxobutanoic acid (PPO). We demonstrated that GLA and PPO disturb ependymal wall integrity in the ventricular-subventricular zone (V-SVZ) and alter the neuro-glial differentiation of neural stem cells. GLA and PPO impaired the formation of cilia, with reduced Celsr2 expression after PPO exposure. GLA promoted the differentiation of neuronal and oligodendroglial cells while PPO increased B1 cell population and impaired neuronal fate of neural stem cells. These results confirm our previous in vivo report that developmental exposure to GLA alters neurogenesis in the SVZ, and neuroblast migration along the rostral migratory stream. They also highlight the importance of investigating the toxicity of pesticide degradation products. Indeed, not only GLA, but also its metabolite PPO disrupts V-SVZ homeostasis and provides a novel cellular mechanism underlying GLA-induced neurodevelopmental toxicity. Furthermore, we were able to demonstrate a neurotoxic activity of a metabolite of GLA different from that of GLA active substance for the very first time

Topics: Glufosinate-ammonium, Pesticide, Neural stem cells, Subventricular zone, Neurotoxicity, [CHIM]Chemical Sciences
Publisher: 'Elsevier BV'
Year: 2018
DOI identifier: 10.1016/j.neuro.2018.10.001
OAI identifier: oai:HAL:hal-02067293v1
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