Primary neuronal-astrocytic co-culture platform for neurotoxicity assessment of di-(2-ethylhexyl) phthalate.
Primary neuronal-astrocytic co-culture platform for neurotoxicity assessment of di-(2-ethylhexyl) phthalate.
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DOI：
10.1016/s1001-0742(13)60504-5
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发表时间：
2014-05
影响因子：
6.9
通讯作者：
Yang Wu;Ke Li;Haoxiao Zuo;Ye Yuan;Yi Sun;Xu Yang
中科院分区：
文献类型：
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作者：
Yang Wu;Ke Li;Haoxiao Zuo;Ye Yuan;Yi Sun;Xu Yang
聚氯乙烯（PVC）等塑料广泛用于许多室内建筑环境;然而，其未结合的化学物质，如邻苯二甲酸二（2-乙基己基）酯（DEHP），可能会渗入周围环境。本研究通过测定接触化学品后小鼠脑组织中DEHP的精确含量，来评价DEHP对中枢神经系统的影响，以评估具体的接触范围。原代神经元-星形胶质细胞共培养系统被用作DEHP化学危害识别的体外模型。氧化应激被假设为一个可能的机制，因此总活性氧（ROS）浓度被确定为氧化应激的生物标志物。此外，NeuriteTracer是一种带有ImageJ的神经突追踪插件，用于开发神经毒性测定，以提供神经参数的定量测量，例如神经元数量、神经元计数和神经突长度，所有这些都可以指示神经毒性作用。结果表明，在1 nmol/L DEHP暴露下，ROS浓度显著增加，表明神经元-星形胶质细胞培养物因暴露于DEHP而受损。作为响应，星形胶质细胞增殖（神经胶质增生）被启动，作为一种机制，以维持神经元的稳态环境，并保护神经元免受有毒化学物质的影响。有必要评估DEHP在动物体内的累积效应，以评价在室内环境中暴露于DEHP对人体神经系统的可能吸收和影响。
Plastics such as polyvinyl chlorides (PVC) are widely used in many indoor constructed environments; however, their unbound chemicals, such as di-(2-ethylhexyl) phthalates (DEHP), can leach into the surrounding environment. This study focused on DEHP's effect on the central nervous system by determining the precise DEHP content in mice brain tissue after exposure to the chemical, to evaluate the specific exposure range. Primary neuronal-astrocyte co-culture systems were used asin vitromodels for chemical hazard identification of DEHP. Oxidative stress was hypothesized as a probable mechanism involved, and therefore the total reactive oxygen species (ROS) concentration was determined as a biomarker of oxidative stress. In addition, NeuriteTracer, a neurite tracing plugin with ImageJ, was used to develop an assay for neurotoxicity to provide quantitative measurements of neurological parameters, such as neuronal number, neuron count and neurite length, all of which could indicate neurotoxic effects. The results showed that with 1 nmol/L DEHP exposure, there was a significant increase in ROS concentrations, indicating that the neuronal-astrocyte cultures were injured due to exposure to DEHP. In response, astrocyte proliferation (gliosis) was initiated, serving as a mechanism to maintain a homeostatic environment for neurons and protect neurons from toxic chemicals. There is a need to assess the cumulative effects of DEHP in animals to evaluate the possible uptake and effects on the human neuronal system from exposure to DEHP in the indoor environment.