Bisphenol analogues induced social defects and neural impairment in zebrafish

Abstract

There is evidence in humans that endocrine disrupting chemicals exposure, such as bisphenol A (BPA), is tied to social behavior impacts when evaluated in early life stage. However, the potential social impact of BPA alternatives and its association with central nervous system (CNS) is poorly understood. Here, we performed behavioral test for zebrafish that are continuously exposed to environmental relevant concentrations (5 and 500 ng/L) of BPA, BPF, and BPAF since embryonic stage. Surprisingly, significant social behavior defects, including increased social distance and decreased contact time, were identified in zebrafish treated by 500 ng/L BPAF and BPA. These behavioral changes were accompanied by apparent histological injury, microglia activation, enhanced apoptosis and neuron loss in brain. The gut-brain transcriptional profile showed that genes involved in neuronal development pathways were up-regulated in all bisphenol analogs treatments, indicating a protective phenotype of CNS; however, these pathways were inhibited in gut. Besides, a variety of key regulators in the gut-brain regulation were identified based on protein interaction prediction, such as rac1-limk1, insrb1 and fosab. These findings implicated that the existence of bisphenol analogues in water would influence the social life of fish, and revealed a potential role of gut-brain transcriptional alteration in mediating this effect.

Keywords: Bisphenol analogues; Gut-brain transcriptional changes; Neural damage; Social behavior defect; Zebrafish.