Multiple effects of the herbicide glufosinate-ammonium and its main metabolite on neural stem cells from the subventricular zone of newborn mice
| Autor: | Anthony Laugeray, Camille Mougin, Valérie F. J. Quesniaux, Thierry Gefflaut, Céline Montécot-Dubourg, Stéphane Mortaud, Vanessa Larrigaldie, Olivier Richard, Justyne Feat-Vetel, Ameziane Herzine, Géraldine Meyer-Dilhet |
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| Přispěvatelé: | Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de Clermont-Ferrand (ICCF), SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Université d'Orléans (UO), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Rostral migratory stream Cell Survival Subventricular zone Metabolite Population Toxicology Glufosinate-ammonium 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Prosencephalon Neuroblast migration Lateral Ventricles medicine Neurotoxicity Animals [CHIM]Chemical Sciences cardiovascular diseases education Cells Cultured Neural stem cells education.field_of_study Dose-Response Relationship Drug Herbicides General Neuroscience Aminobutyrates Neurogenesis Glutamate receptor nutritional and metabolic diseases Neural stem cell 3. Good health Cell biology Mice Inbred C57BL Pesticide 030104 developmental biology medicine.anatomical_structure chemistry Animals Newborn nervous system lipids (amino acids peptides and proteins) 030217 neurology & neurosurgery hormones hormone substitutes and hormone antagonists |
| Zdroj: | NeuroToxicology NeuroToxicology, 2018, 69, pp.152-163. ⟨10.1016/j.neuro.2018.10.001⟩ NeuroToxicology, Elsevier, 2018, 69, pp.152-163. ⟨10.1016/j.neuro.2018.10.001⟩ |
| ISSN: | 0161-813X |
| DOI: | 10.1016/j.neuro.2018.10.001⟩ |
| Popis: | International audience; The 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. |
| Databáze: | OpenAIRE |
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