Neural stem cell-based in vitro bioassay for the assessment of neurotoxic potential of water samples

Intensive agriculture activities, industrialization and growing numbers of wastewater treatment plants along river banks collectively contribute to the elevated levels of neurotoxic pollutants in natural water reservoirs across Europe. We established an in vitro bioassay based upon neural stem cells isolated from the subventricular zone of the postnatal mouse to evaluate the neurotoxic potential of raw wastewater, treated sewage effluent, groundwater and drinking water. The toxic potential of water samples was evaluated employing viability, proliferation, differentiation and migration assays. We found that raw wastewater could reduce the viability and proliferation of neural stem cells, and decreased the neuronal and astrocyte differentiation, neuronal neurite growth, astrocyte growth and cell migration. Treated sewage water also showed inhibitory effects on cell proliferation and migration. Our results indicated that relatively high concentrations of nitrogenous substances, pesticides, mercuric compounds, bisphenol-A, and phthalates, along with some other pollutants in raw wastewater and treated sewage water, might be the reason for the neuroinhibitory effects of these water samples. Our model successfully predicted the neurotoxicity of water samples collected from different sources and also revealed that the incomplete removal of contaminants from wastewater can be problematic for the developing nervous system. The presented data also provides strong evidence that more effective treatments should be used to minimize the contamination of water before release into major water bodies which may be considered as water reservoirs for human usage in the future.     

评估斑马鱼胚胎毒性试验在农药危害筛选中的应用

考虑到人类社会中大量使用化学物质,想要准确有效地评估这些化学物质对人类和生态受体的潜在风险,研发有效的手段和方法是至关重要的。鱼胚胎急性毒性试验是其中一种工具,已表现出与幼鱼急性毒性标准试验的预测结果高度吻合,而幼鱼试验对资源消耗更多。然而,也有证据表明,对于某些类型的化学物质,包括神经毒素,鱼类胚胎的敏感性低于幼鱼。本文利用已发表的斑马鱼胚胎毒性数据,与3种常用检测用鱼幼鱼(虹鳟鱼、蓝鳃太阳鱼、羊鲷)的半致死浓度50%(LC₅₀)数据进行比较,研究了鱼类胚胎对农药危害评估的效用。在将农药视为单因素的情况下,斑马鱼胚胎和幼鱼毒性数据相关性较差,差异显著(r²=0.28;p2=0.64;p 精选自Glaberman, S., Padilla, S. and Barron, M. G. (2017), Evaluating the zebrafish embryo toxicity test for pesticide hazard screening. Environmental Toxicology and Chemistry, 36: 1221–1226. doi: 10.1002/etc.3641
详情请见http://onlinelibrary.wiley.com/doi/10.1002/etc.3641/full
     

Identification of differentially expressed genes response to TCDD in rat brain after long-term low-dose exposure

Several cohort studies have reported that dioxin and dioxin-like polychlorinated biphenyls might impair the nervous system and lead to neurological or neurodegenerative diseases in the elder people, but there is limited research on the involved mechanism. By using microarray analysis, we figured out the differentially expressed genes between brain samples from SD rats after low-dose(0.1 μg/(kg?bw)) dioxin exposure for six months and controls. To investigate the function changes in the course of dioxin exposure, Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the differentially expressed genes. And the changes of several picked genes have been verified by real-time PCR. A total of 145 up-regulated and 64 down-regulated genes were identified. The metabolic processes, interleukin-1 secretion and production were significantly associated with the differentially expressed genes. And the genes regulated by dioxin also clustered to cholinergic synapse and long-term potentiation. Candidate biomarker genes such as egr1, gad2, gabrb3, abca1, ccr5 and pycard may be toxicological targets for dioxin. Furthermore, synaptic plasticity and neuro-immune system may be two principal affected areas by dioxin.