Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, Saarbrücken, D-66123, Germany; Working Group Enteric Nervous System, University of Applied Sciences Kaiserslautern, Campus Zweibrücken, 66482, Germany; Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, 54000, Pakistan.
Department of Zoology, University of Balochistan, Quetta, 87550, Pakistan.
Environ Pollut. 2021 Feb 1;270:116179. doi: 10.1016/j.envpol.2020.116179. Epub 2020 Dec 5.
The developing nervous system is highly vulnerable to environmental toxicants especially pesticides. Glyphosate pesticide induces neurotoxicity both in humans and rodents, but so far only when exposed to higher concentrations. A few studies, however, have also reported the risk of general toxicity of glyphosate at concentrations comparable to allowable limits set up by environmental protection authorities. In vitro data regarding glyphosate neurotoxicity at concentrations comparable to maximum permissible concentrations in drinking water is lacking. In the present study, we established an in vitro assay based upon neural stem cells (NSCs) from the subventricular zone of the postnatal mouse to decipher the effects of two maximum permissible concentrations of glyphosate in drinking water on the basic neurogenesis processes. Our results demonstrated that maximum permissible concentrations of glyphosate recognized by environmental protection authorities significantly reduced the cell migration and differentiation of NSCs as demonstrated by the downregulation of the expression levels of the neuronal ß-tubulin III and the astrocytic S100B genes. The expression of the cytoprotective gene CYP1A1 was downregulated whilst the expression of oxidative stresses indicator gene SOD1 was upregulated. The concentration comparable to non-toxic human plasma concentration significantly induced cytotoxicity and activated Ca signalling in the differentiated culture. Our findings demonstrated that the permissible concentrations of glyphosate in drinking water recognized by environmental protection authorities are capable of inducing neurotoxicity in the developing nervous system.
发育中的神经系统对环境毒物,尤其是农药,非常敏感。草甘膦农药在人类和啮齿动物中都能引起神经毒性,但迄今为止,只有在接触更高浓度时才会出现这种情况。然而,一些研究也报告了草甘膦在与环境保护局设定的允许浓度相当的浓度下产生一般毒性的风险。目前,关于与饮用水中最大允许浓度相当的草甘膦浓度的体外神经毒性数据还很缺乏。在本研究中,我们建立了一种基于新生小鼠侧脑室下区神经干细胞(NSC)的体外分析方法,以阐明饮用水中两种最大允许浓度的草甘膦对基本神经发生过程的影响。我们的结果表明,环境保护局认可的最大允许浓度的草甘膦显著降低了 NSCs 的细胞迁移和分化,这表现为神经元 ß-微管蛋白 III 和星形胶质细胞 S100B 基因的表达水平下调。细胞保护基因 CYP1A1 的表达下调,而氧化应激指标基因 SOD1 的表达上调。与非毒性人血浆浓度相当的浓度则显著诱导分化培养中的细胞毒性和钙信号激活。我们的研究结果表明,环境保护局认可的饮用水中草甘膦的允许浓度能够在发育中的神经系统中引起神经毒性。