title: Characterization of seizures induced by acute exposure to an organophosphate herbicide, glufosinate-ammonium.
abstract: Glufosinate-ammonium (GLA), the active component of a widely used herbicide, induces convulsions in rodents and humans. In mouse, intraperitoneal treatment with 75 mg/kg GLA generates repetitive tonic-clonic seizures associated with 100% mortality within 72 h after treatment. In this context, we characterized GLA-induced seizures, their histological consequences and the effectiveness of diazepam treatment. Epileptic discharges on electroencephalographic recordings appeared simultaneously in the hippocampus and the cerebral cortex. Diazepam treatment at 6 h immediately stopped the seizures and prevented animal death. However, intermittent seizures were recorded on electroencephalogram from 6 h after diazepam treatment until 24 h, but had disappeared after 15 days. In our model, neuronal activation (c-Fos immunohistochemistry) was observed 6 h after GLA exposure in the dentate gyrus, CA1, CA3, amygdala, piriform and entorhinal cortices, indicating the activation of the limbic system. In these structures, Fluoro-Jade C and Cresyl violet staining did not show neuronal suffering. However, astroglial activation was clearly observed at 24 h and 15 days after GLA treatment in the amygdala, piriform and entorhinal cortices by PCR quantitative, western blot and immunohistochemistry. Concomitantly, glutamine synthetase mRNA expression (PCR quantitative), protein expression (western blot) and enzymatic activity were upregulated. In conclusion, our study suggests that GLA-induced seizures: (a) involved limbic structures and (b) induced astrocytosis without neuronal degeneration as an evidence of a reactive astrocyte beneficial effect for neuronal protection.
authors.affiliation: aFrench Armed Forces Biomedical Research Institute, Brétigny-sur-Orge bUMR7355, CNRS, Orléans cDepartment of Experimental and Molecular Immunology and Neurogenetics, University of Orleans dDepartment of Genetics, Regional Hospital, Orléans eCNRS, UMR-5203, Institute for Functional Genomics, Montpellier, France fDepartments of Internal Medicine Specialities and of Pathology-Immunology, Division of Rheumatology, University of Geneva School of Medicine, Geneva, Switzerland.
authors.forename: André-Guilhem
authors.initials: AG
authors.lastname: Calas
authors.forename: Olivier
authors.initials: O
authors.lastname: Perche
authors.forename: Olivier
authors.initials: O
authors.lastname: Richard
authors.forename: Astrid
authors.initials: A
authors.lastname: Perche
authors.forename: Arnaud
authors.initials: A
authors.lastname: Pâris
authors.forename: Fabien
authors.initials: F
authors.lastname: Lauga
authors.forename: Ameziane
authors.initials: A
authors.lastname: Herzine
authors.forename: Jennifer
authors.initials: J
authors.lastname: Palomo
authors.forename: Marie-Yvonne
authors.initials: MY
authors.lastname: Ardourel
authors.forename: Arnaud
authors.initials: A
authors.lastname: Menuet
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mortaud
authors.forename: Jacques
authors.initials: J
authors.lastname: Pichon
authors.forename: Céline
authors.initials: C
authors.lastname: Montécot-Dubourg
mesh_terms: D000613:Aminobutyrates / Q000633:toxicity*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage; D001253:Astrocytes / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D003975:Diazepam / Q000008:administration & dosage; D004569:Electroencephalography; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects; D010755:Organophosphates / Q000633:toxicity*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000613:Aminobutyrates; D000927:Anticonvulsants; D006540:Herbicides; D010755:Organophosphates; D016760:Proto-Oncogene Proteins c-fos; C003121:phosphinothricin; D005974:Glutamate-Ammonia Ligase; D003975:Diazepam