The Neurotoxicity,susceptibility And Mechanism Of TBBPA-DHEE Exposure In Zebrafish

Tetrabromobisphenol A-bis(2-hydroxyethyl)ether(TBBPA-DHEE)is one of the main derivatives of TBBPA,which has highly similar structure.It has been detected in various environmental media and organisms,and has potential neurotoxicity.However,the toxic of TBBPA-DHEE on aquatic organisms haven't been reported.In this study,zebrafish were selected as the research subject to explore the neurotoxicity and its mechanism of low-dose TBBPA-DHEE exposure to juvenile and adult zebrafish,and to reveal the neurotoxicity susceptibility of zebrafish in different periods and in different sexes.It could provide scientific basis for ecological risk and health effect evaluation of these new environmental pollutants.The main research contents are as follows:(1)Neurotoxicity and its molecular mechanism of exposure to TBBPA-DHEE in juvenile zebrafish.Results showed that exposure to low dose TBBPA-DHEE could cause neurotoxicity,and female and male zebrafish showed different toxic effects.TBBPA-DHEE could significantly reduce the swimming velocity,maximum acceleration and cumulative duration of high-speed mobility,significantly increase the cumulative duration of low-speed mobility and average social distance of each two fish,and significantly reduce the contents of ATP,glutamate and Ca²⁺,which affected the behavior of juvenile zebrafish.It could cause brain tissue damage for young female and male zebrafish.Molecular mechanism studies showed that juvenile female and male zebrafish have different molecular mechanisms of neurotoxicity.For juvenile female zebrafish,TBBPA-DHEE could significantly affect the expressions of behavioral and development-related genes.The potential mechanism of neurotoxicity could be that it interfered with the feedback regulation of nerves by affecting the related genes expressions in the signaling pathways such as Ca²⁺signaling,Wnt signaling and synapses.For juvenile male zebrafish,TBBPA-DHEE could significantly affect the expressions of behaviors and developmental related genes.The potential mechanism of neurotoxicity may be through affecting the related genes expression in hormones and neuro related genes.(2)Neurotoxicity and its molecular mechanism of exposure to TBBPA-DHEE in adult zebrafish.Results showed that exposure to low dose TBBPA-DHEE could induce neurotoxicity in adult zebrafish,which showed the same behavioral effect as that in juvenile zebrafish,and female and male zebrafish showed different toxic effects.It could cause minor brain tissue damage in male zebrafish.Molecular mechanism studies showed that adult female and male zebrafish displayed different molecular mechanism of neurotoxicity.For adult female zebrafish,TBBPA-DHEE treatment could significantly affect the behavior and development related genes expressions,its potential mechanism could be through affecting the related genes expressions in hormones,Ca²⁺signaling pathways and synaptic pathways.For adult male zebrafish,TBBPA-DHEE could significantly affect their behavior and neuro-related genes expressions.The potential mechanism of neurotoxicity could through inhibiting the Ca²⁺signal transduction by affecting the expressions of related genes in neuro-synapses,Ca²⁺signaling and MAPK signaling pathways.(3)Study on the susceptibility of TBBPA-DHEE exposure to neurotoxicity in zebrafish.Results showed that female zebrafish were more susceptible to TBBPA-DHEE exposure than male zebrafish for juvenile zebrafish.For adult zebrafish,there was no significant difference in neurotoxicity between female and male zebrafish exposed to TBBPA-DHEE.For female and male zebrafish,exposure to TBBPA-DHEE was more susceptible to neurotoxicity in juvenile zebrafish than in adult zebrafish.