| Bisphenol A,a kind of endocrine disrupting chemicals(EDCs),is one of the highest production volume synthetic chemicals in the world.BPA is mainly used for the production of polycarbonate and epoxy resin,and then used in industrial production.Many experiments have reported the adverse effects of BPA exposure on animals,such as cancer,infertility,reproductive problem,cardiovascular disease,obesity and nerve problem among others.Considering the known and potential toxic effects of bisphenol A on humans and many countries(including China)have clearly prohibited the use of bisphenol A in some industrial production,which has stimulated the use of bisphenol A substitutes in the industry for production.However,zebrafish exposure model studies have also reported that BPS can interfere functions of fish nervous system.However,whether BPS can be used as a safe alternative to BPA for brain function in mammals is still elusive.The juvenile is a critical period for brain development,and the nervous system during this phase is easily disturbed by the external environment.In addition,the hormone levels tend to be stable during this period,which can be used as a good window to study the effects of environmental estrogen exposure on brain function.In this study,C57BL/6J juvenile mice(P21-P49)were used as animal models for different doses of BPA and BPS exposure(0.1 mg/kg/d,1 mg/kg/d).Different behavioral paradigms,including open field test,tail suspension test,forced swimming test,fear test and three-chamber social test,were used to evaluate the effects of juvenile bisphenol exposure on the emotional and social behavior of mice.Results showed that,compared with the control group,0.1 mg/kg/d and 1mg/kg/d BPA exposure and 1 mg/kg/d BPS all caused anxiety-like behaviors and social deficits in mice,while there were no changes in 0.1 mg/kg/d BPS exposure group.In addition,1 mg/kg/d BPA and BPS exposure increased the immobility time of mice in both tail suspension test and forced swimming test,which exhibited depressive-like behavior,while 0.1 mg/kg/d BPA and BPS exposure did not.Finally,we assessed the conditioned fear behavior of the mice by foot shock,it was found that there was no change in the behavioral performance during the conditioned fear period in all groups.However,after 24 hours,1mg/kg/d BPA exposure significantly enhanced fear memory of mice,while weakened the neutral memory.In addition,although BPS exposure under low level showed no effects on mouse behaviors,high dose BPS,same to BPA,significantly induced behavioral dysfunctions and there were no significant differences between BPA and BPS exposure groups.The behavioral results also indicated that BPA and BPS exposure could cause emotional abnormalities and impaired social behavior in mice in a dose-dependent manner.Previous studies have confirmed that the hyperactivity of basolateral amygdala(BLA)brain region is related to the impaired emotional and social behaviors.In the present study,the electrophysiological results indicated that,except 0.1 mg/kg/d BPS exposure group,both BPA and 1 mg/kg/d BPS exposure groups significantly enhanced the local field potential(LFP)energy power(including theta oscillation,gamma oscillation)compared with the control group,and the firing rates of neurons in the BLA were also significantly increased.Meanwhile,the western blotting results showed that the expression of excitatory glutamate receptors in BLA,including GLUR1,GLUR2 and NR2,were significantly increased after juvenile BPA and BPS exposure.Therefore,those results all indicated that juvenile BPA and BPS exposure would induce the excessive activation of BLA and the occurrence of disrupted emotional and social behaviors. |
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