title: Neurotoxicity of a Biopesticide Analog on Zebrafish Larvae at Nanomolar Concentrations.
abstract: Despite the ever-increasing role of pesticides in modern agriculture, their deleterious effects are still underexplored. Here we examine the effect of A6, a pesticide derived from the naturally-occurring α-terthienyl, and structurally related to the endocrine disrupting pesticides anilinopyrimidines, on living zebrafish larvae. We show that both A6 and an anilinopyrimidine, cyprodinyl, decrease larval survival and affect central neurons at micromolar concentrations. Focusing on a superficial and easily observable sensory system, the lateral line system, we found that defects in axonal and sensory cell regeneration can be observed at much lower doses, in the nanomolar range. We also show that A6 accumulates preferentially in lateral line neurons and hair cells. We examined whether A6 affects the expression of putative target genes, and found that genes involved in apoptosis/cell proliferation are down-regulated, as well as genes reflecting estrogen receptor activation, consistent with previous reports that anilinopyrimidines act as endocrine disruptors. On the other hand, canonical targets of endocrine signaling are not affected, suggesting that the neurotoxic effect of A6 may be due to the binding of this compound to a recently identified, neuron-specific estrogen receptor.
authors.affiliation: U1198 MMDN (Molecular Mechanisms of Neurodegenerative Diseases), Inserm (National Institute for Health and Medical Research), 34095 Montpellier, France. a7mednas@gmail.com.|BioCampus, University of Montpellier, 34095 Montpellier, France. a7mednas@gmail.com.|EPHE (Ecole Pratique des Hautes Etudes), 75007 Paris, France. a7mednas@gmail.com.|Laboratory of Environment Biomonitoring, Faculty of Sciences of Bizerta, University of Carthage, 7021 Zarzouna, Tunisia. a7mednas@gmail.com.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Nasri
authors.affiliation: U1198 MMDN (Molecular Mechanisms of Neurodegenerative Diseases), Inserm (National Institute for Health and Medical Research), 34095 Montpellier, France. audrey-valverde@hotmail.fr.|BioCampus, University of Montpellier, 34095 Montpellier, France. audrey-valverde@hotmail.fr.|EPHE (Ecole Pratique des Hautes Etudes), 75007 Paris, France. audrey-valverde@hotmail.fr.
authors.forename: Audrey J
authors.initials: AJ
authors.lastname: Valverde
authors.affiliation: IBC (Computational Biology Institute), CNRS (National Center for Scientific Research), University of Montpellier, 860 rue Saint Priest, 34095 Montpellier, France. daniel.roche@lirmm.fr.|CRBM (Research Center for Cell Biology in Montpellier), UMR 5237, CNRS, 1919 route de Mende, 34293 Montpellier, France. daniel.roche@lirmm.fr.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Roche
authors.affiliation: U1198 MMDN (Molecular Mechanisms of Neurodegenerative Diseases), Inserm (National Institute for Health and Medical Research), 34095 Montpellier, France. desrumauxcatherine@yahoo.com.|BioCampus, University of Montpellier, 34095 Montpellier, France. desrumauxcatherine@yahoo.com.|EPHE (Ecole Pratique des Hautes Etudes), 75007 Paris, France. desrumauxcatherine@yahoo.com.
authors.forename: Catherine
authors.initials: C
authors.lastname: Desrumaux
authors.affiliation: MGX (Montpellier GenomiX), BioCampus, University of Montpellier, 34095 Montpellier, France. philippe.clair@univ-montp2.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Clair
authors.affiliation: CRBM (Research Center for Cell Biology in Montpellier), UMR 5237, CNRS, 1919 route de Mende, 34293 Montpellier, France. hamouda.beyrem@gmail.com.
authors.forename: Hamouda
authors.initials: H
authors.lastname: Beyrem
authors.affiliation: CPBS (Center for Study of Pathogens and Biotechnologies for Health), FRE 3689, CNRS, University of Montpellier, 1919 route de Mende, 34293 Montpellier, France. laurent.chaloin@cpbs.cnrs.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Chaloin
authors.affiliation: U1198 MMDN (Molecular Mechanisms of Neurodegenerative Diseases), Inserm (National Institute for Health and Medical Research), 34095 Montpellier, France. alain.ghysen@univ-montp2.fr.|BioCampus, University of Montpellier, 34095 Montpellier, France. alain.ghysen@univ-montp2.fr.|EPHE (Ecole Pratique des Hautes Etudes), 75007 Paris, France. alain.ghysen@univ-montp2.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Ghysen
authors.affiliation: U1198 MMDN (Molecular Mechanisms of Neurodegenerative Diseases), Inserm (National Institute for Health and Medical Research), 34095 Montpellier, France. veronique.perrier@umontpellier.fr.|BioCampus, University of Montpellier, 34095 Montpellier, France. veronique.perrier@umontpellier.fr.|EPHE (Ecole Pratique des Hautes Etudes), 75007 Paris, France. veronique.perrier@umontpellier.fr.
authors.forename: Véronique
authors.initials: V
authors.lastname: Perrier
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D061046:Biological Control Agents / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D052244:Endocrine Disruptors / Q000633:toxicity*; D005786:Gene Expression Regulation; D007814:Larva / Q000187:drug effects*; D053403:Lateral Line System / Q000187:drug effects*; D008465:Mechanoreceptors / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D011743:Pyrimidines / Q000633:toxicity*; D011744:Pyrimidinones / Q000633:toxicity*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects; D013876:Thiophenes / Q000737:chemistry / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology*
chemical_list: C000616933:2-(2'-thienyl)-5-(4''-(2''-aminopyrimidyl)thiophene; D061046:Biological Control Agents; D052244:Endocrine Disruptors; D011743:Pyrimidines; D011744:Pyrimidinones; D011960:Receptors, Estrogen; D013876:Thiophenes; C019101:alpha-terthienyl; C108338:cyprodinil
keywords: hair cells; mechanosensory organ; mechanosensory system; posterior lateral line; pyrimidine; α-terthienyl