Effects of Dioxin and OH-PCB on Neural Differentiation from Mouse ES cells
Development of the brain in the neonatal period is susceptible to maternal exposure to environmental chemicals, such as dioxins and polychlorinated biphenyls (PCBs), but the toxicity mechanisms are largely unknown. In this study, we investigated effects of these chemicals on neurogenesis by using in vitro system for the differentiation from mouse embryonic stem (ES) cell to neural cell line. Neural differentiation form embryoid body (EB) is known to be induced by retinoic acid. During this differentiation period, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 4-hydroxylated-2,3,3,4,5,5-hexa chlorinated biphenyl (OH-PCB) were added into the cell culture medium. The differentiation process from ES cells to neural lineage cells was monitored by real-time RT-PCR at several differentiating points using respective neural cell markers. The expression of oligodendrocyte-specific markers, olig1 and olig2, decreased by TCDD and OH-PCB, while that of neuron-specific marker MAP2 and astrocyte-specific marker GFAP did not, suggesting that TCDD and OH-PCB suppress oligodendrocyte differentiation form EB. Moreover, high-throughput multi-channel imaging analysis was used to investigate morphological changes in oligodendrocytes and neurons. Among several morphological parameters, the neurite extension of MAP2-positive neuron was suppressed by exposure of TCDD, but no changes were detected in that of oligodendrocyte-specific marker positive cells. These results suggest that TCDD and OH-PCB may perturb differentiation of several neural cells during the embryonic stage.
Miyazaki W Nagano R Sone H Tohyama C Ohsako S
Laboratory of Environmental Health Sciences,Center for Disease Biology and Integrative Medicine,Grad Research Center for Environmental Risk,National Institute for Environmental Studies,Tsukuba,Japan
国际会议
北京
英文
1-4
2009-08-24(万方平台首次上网日期,不代表论文的发表时间)