Calas André-Guilhem, Perche Olivier, Richard Olivier, Perche Astrid, Pâris Arnaud, Lauga Fabien, Herzine Ameziane, Palomo Jennifer, Ardourel Marie-Yvonne, Menuet Arnaud, Mortaud Stéphane, Pichon Jacques, Montécot-Dubourg Céline
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.
Neuroreport. 2016 May 4;27(7):532-41. doi: 10.1097/WNR.0000000000000578.
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.
草铵膦铵盐（GLA）是一种广泛使用的除草剂的活性成分，可在啮齿动物和人类中诱发惊厥。在小鼠中，腹腔注射75mg/kg GLA会引发重复性强直阵挛性癫痫发作，治疗后72小时内死亡率达100%。在此背景下，我们对GLA诱发的癫痫发作、其组织学后果以及地西泮治疗的有效性进行了表征。脑电图记录显示癫痫放电同时出现在海马体和大脑皮层。地西泮在6小时时进行治疗可立即停止癫痫发作并防止动物死亡。然而，地西泮治疗后6小时至24小时期间脑电图记录到间歇性癫痫发作，但15天后消失。在我们的模型中，GLA暴露6小时后在齿状回、CA1、CA3、杏仁核、梨状皮质和内嗅皮质中观察到神经元激活（c-Fos免疫组织化学），表明边缘系统被激活。在这些结构中，氟玉髓C和甲酚紫染色未显示神经元受损。然而，通过PCR定量、蛋白质印迹和免疫组织化学在GLA治疗后24小时和15天在杏仁核、梨状皮质和内嗅皮质中清楚地观察到星形胶质细胞激活。同时，谷氨酰胺合成酶mRNA表达（PCR定量）、蛋白质表达（蛋白质印迹）和酶活性上调。总之，我们的研究表明，GLA诱发的癫痫发作：（a）涉及边缘结构；（b）诱导星形细胞增生而无神经元变性，这是反应性星形胶质细胞对神经元保护有益作用的证据。
