| Objective: Study the effects of weaning 4 weeks exposure to bisphenol A(BPA)on the neurobehavioral function.Based to these data,explore the role of ERα mediated protein kinase C/extracellular signal-regulated kinase/cAMP response element binding protein(PKC/ERK/CREB)signaling pathway on the neurobehavioral function impairment,and provide new ideas for the research on mechanism of BPA neurotoxicity.Methods: Healthy pregnant C57BL/6 mice were randomly assigned into control group(drinking water containing 1% absolute ethanol),low BPA group(drinking water containing 0.2 mg/L BPA)and high BPA group(drinking water containing 2 mg/L BPA)(24 mice,each of 8 mice).The gestation 6 days,all pregnant mice drank water containing BPA in different concentrations until the end of lactation.The offspring mice were weaned 21 days after birth.After weaning,mice drank water no containing BPA until weaning 4 weeks.The body weight,food intake and water intake of offspring mice were recorded.The disease,infection and death of offspring mice were observed.After weaning 4 weeks,offspring male mice were subjected to Morris water maze and open field test.Brain tissue was taken,brain weight and bilateral hippocampal weight were weighed,and hippocampal coefficient was calculated.The hippocampal tissues of all offspring male mice were taken and the protein levels of ERa,PKC,ERK,phosphorylated ERK(p-ERK),CREB and phosphorylated CREB(p-CREB)in the hippocampus were detected by Western-blot.Results: 1.No significant difference in weight,food and water intake among each group offspring male mice(P > 0.05).2.No significant difference in brain weight,hippocampal weight and hippocampal coefficient among each group of offspring male mice(P > 0.05).3.In the study period of water maze experiment,compared with the control group,the average distance of offspring male mice search platform in low and high BPA group was significantly prolonged on the 4th and 5th days,the time of search platform in low BPA group was significantly prolonged on the 5th day,and the time of search platform in high BPA group was significantly prolonged on the 4th and 5th days,the above differences were statistically significant(P < 0.05).In the memory period,the number and duration of male offspring crossing the target quadrant in low and high BPA group were significantly less than those in control group,and the number and duration of male offspring crossing the target quadrant in high BPA group were significantly less than those in low BPA group,the differences were statistically significant(P < 0.05).4.In the open field experiment,compared with the control group,the number of buttresses of offspring male mice in low and high BPA groups decreased significantly(P < 0.05),and the central residence time and acceleration of male offspring in low and high BPA groups increased significantly(P < 0.05).Compared with the low BPA group,there was no significant difference in the number of buttresses,central residence time and central acceleration between the high BPA group and the low BPA group(P > 0.05).5.The expression of ERα and PKC protein in offspring male mice of low and high BPA group was significantly lower than that of control group,and the expression of ERα and PKC protein in male offspring of high BPA group was significantly lower than that of low BPA group(P < 0.05).The expression of p-ERK and p-CREB protein and the ratio of p-ERK/ERK and p-CREB/CREB in male offspring of low and high BPA group were significantly lower than those in control group.With the increase of dose,the expression of p-CREB showed a dose-response relationship.The above differences were statistically significant(P < 0.05),but the expression levels of total protein ERK and CREB remained unchanged(P > 0.05).Conclusion: Perinatal exposure to BPA impairs the neurobehavioral function of offspring male mice,including spatial learning and memory function,exploration behavior and anxiety-related behavior,and through ERα mediate PKC/ERK/CREB signaling pathway. |
