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intranasal administration of tetrabromobisphenol A bis(2-hydroxyethyl ether) induces neurobehavioral changes in neonatal Sprague Dawley rats

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Journal of Environmental Sciences 2018年第1期30卷 76-86页

作者： Qian S.Liu Na Liu Zhendong Sun Qunfang Zhou Guibin Jiang State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental Sciences Chinese Academy of Sciences College of Resources and Environment University of Chinese Academy of Sciences School of Life Science Shanxi University

Tetrabromobisphenol A（tbbpa） and its derivatives are now being highly concerned due to their emerging environmental occurrence and deleterious effects on non-target *** the potential neurotoxicity of tbbpa derivatives which has been demonstrated in vitro, what could happen in vivo is worthy of being studied. Tetrabromobisphenol A bis（2-hydroxyethyl ether）（tbbpa-BHEE）, a representative tbbpa derivative, was selected for a21-day exposure experiment on neonatal Sprague Dawley（SD） rats through intranasal administration. The neurobehavioral, histopathological changes, and differentially expressed genes based on RNA microarray were investigated to evaluate the neurological effects of this chemical. The results indicated that tbbpa-BHEE exposure significantly compromised the motor co-ordination performance and the locomotor activities（p 〈 0.05）. The neurobehavioral phenotype could be attributed to the obvious histopathological changes in both cerebrum and cerebellum, such as neural cell swelling, microglial activation and proliferation. A total of 911 genes were up-regulated, whereas 433 genes were down-regulated. Gene set enrichment analysis showed multiple signaling pathways, including ubiquitin-mediated proteolysis and wingless-int（Wnt） signaling pathway etc. were involved due to tbbpa-BHEE exposure. The gene ontology enrichment analysis showed the basic cellular function and the neurological processes like synaptic transmission were influenced. The toxicological effects of tbbpa-BHEE observed in this study suggested the potential neuronal threaten from unintended exposure,which would be of great value in the biosafety evaluation of tbbpa derivatives.

关键词： tbbpa derivatives intranasal administration neurobehavorial test histopathological observation microarray analysis

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