Effects Of Perinatal Exposed To PBDE-209 On Cognitive Function And Emotion In F1 Mice

Objective To explore the effects of perinatally exposed to PBDE-209 on cognitive function and emotion of F1 adult mice.Methods Six week-old ICR mice are putting according to male and female ratio of 1to 2 in one cage,after 1week adaptive breeding.Dividing pregnant mice randomly in corn oil group(10mg/kg BW),100mg/kg PBDE-209 group,300mg/kg PBDE-209 group,500mg/kg PBDE-209 group by body weight.Pregnant mice exposure to PBDE-209 between GD7 to PND21 per day.Recording F0 mice body weight,litter numbers,F1 mice anogenital distance.Elevated plus maze,forced swimming test,open field test,Morris water maze were tested in12 weeks old F1 mice.Histology in hippocampal CA3 areas were observed by light microscope and electron microscope.The levels of ER?(estrogen receptor-?),ER?(estrogen receptor-?),GPR30(G protein-coupled receptor 30),CREB(c AMP responsive element-binding protein)and p CREB in F1 mice hippocampi were analysed by Western blotting.Immunohistochemistry were used to observe the expression status of ER?,ER?,GPR30.RT-PCR(real-time polymerase chain reaction)were used to observe the m RNA expression levels of ER?,ER?,GPR30,CREB.Results Compared with the control,male mice 100mg/kg group anogenital distance increased significantly(P<0.05),female mice 100mg/kg group and 300mg/kg group increased significantly(P <0.05).Behavioral experiments showed: The male mice are exposed to PBDE-209 escape latency longer than control group,but did not have significant difference.The female mice are exposed to PBDE-209 escape latency significantly more longer than control groups(P <0.05).The female mice control group spent more time in targer quadurant than exposed group(P <0.05).The platform crossing numbers did not have significant difference between control group with exposed group in spatial probe(P >0.05).Center distance,center entries,spent in center had a significant difference between male 500mg/kg group and control group in open field test(P <0.05).Male 300mg/kg group feces numberssignificantly decreased compare with control group(P <0.05).Female 500mg/kg group grooming,stand and feces numberssignificantly decreased compare with control group(P <0.05).Elevated plus maze female 100mg/kg group and 500mg/kg group enter close arms times more than control group(P <0.05),spent in close arm longger than control group(P <0.05),spent in open arm shorter than control group(P <0.05).Female exposure group immobility time significantly increased in forced swimming test,compare with control group.The neuropathological changes were characterized by HE stain,decreased neuron number,worse cell morphology in the CA3 field of hippocampus in exposure group.Control group of nerve cells rich in mitochondria,the cell structure is normal.Exposure group vacuolar degeneration of mitochondria,rough endoplasmic reticulum,fewer synaptic vesicles,the macula densa damaged.We found the expression status of ER? in cell membrane and nucleus by optical microscope using IHC technique.The concentrations of E2 in serum were significantly decreased in male 100mg/kg and 500mg/kg exposure group(P <0.05),not altered significantly among the female,compare with control group.Testosterone decreased significantly In male and female 300mg/kg,500 mg/kg group.(P <0.05)Western blot shows ER?/actin ratio decreased significantly in male exposure group,compared with controls group.ER?/actin ratio significantly decreased and GPR30/acting ratio significantly increased in male 500mg/kg group.ER?/acting ratio significantly increased in female 300mg/kg 500mg/kg group,ER?/acting and GRP30/acting ratio significantly decreased in female exposure group,p CREB/CREB ratio significantly decreased in female 300mg/kg 500mg/kg,compare with control group.There was significant difference in expression of ER? m RNA between male300mg/kg group and control group.There was significant difference in expression of GPR30 m RNA between male 500mg/kg group and control group.ER?,ER?,CREB m RNA decreased significantly in female 100mg/kg group,compare with control group.Conclusion Perinatal exposure PBDE-209 causing offspring cognitive function and emotion impairment by damage synaptic plasticity via ER regulating CREB phosphorylation.