RESUMO
Objective To explore the changes of pubescent immune response in the schizophrenia offspring induced by poly(I:C) during pregnancy and the effects on white matter.Methods The obtained pregnant rats were randomly divided into model group(n=6) and control group (n=5), receiving either poly (I:C) at a dose of 10 mg/kg diluted in 0.9％ NaC1 solution or vehicle solution alone (sterile pyrogen-free 0.9％ NaC1) on gestation day 9 (GD9).Immunohistochemical technique(IHC) was applied to detect the changes of microglias and astrocytes in the prefrontal cortex(PFC) and hippocampus(HC) of partly offsprings in the two groups at the sixth week,as well as Luxol fast blue(LFB) for the changes of white matter.The other offsprings of each group were selected for behavioral assessment at the eighth week.Results The results of prepulse inhibition test showed that PP2, PP4 and PP8 of model groups were significantly lower than that of the control group at young adult(P＜0.01).In passive avoidance test, and the T1 results of model group were significantly higher than those of the control group, the T results of model group were lower than those of control group (P＜ 0.01).Immunohistochemical results indicated that the number of microglias in the model group((264±33)/mm2, (271 ±38)/mm2) was significantly increased in PFC and HC than that in the control group((140±29)/mm2, (169±37)/mm2, P＜0.05) ,which was accompanied with significant morphological changes, while the OD value of astrocyte protein expression in the frontal lobe and hippocampus had no obvious difference between the model group and control group(P＞0.05).The OD value of LFB staining for myelin in the model group(0.29±0.02) was significantly decreased compared with that in the control group(0.33±0.03)(P＜0.01).Conclusion The young adult offsprings with prenatal infection present obvious schizophrenia-like behavior, meanwhile, the microglias activation and demyelination changes in white matter are observed,which provides more evidence for the relationship between immune response and white matter in the pathogenesis of schizophrenia.
RESUMO
Objective By analyzing the changes in behavior and the myelin basic protein (MBP) of the offspring in adult that treated with Poly(I∶C) during pregnancy,and to understand the role of white matter abnormalities in the abnormal behavior of the offspring induced by infection in maternal hosts.Methods Two models maternal female rats were given Poly(I∶ C) with 5 mg/kg and 10mg/kg respectively during the early pregnancy,and control maternal female rats was administered 5 mg/kg saline.The prepulse inhibition test,passive avoidance test and active avoidance test were used to evaluate schizophrenia like behaviors for each groups offspring in 8 weeks,and the expression of MBP was detected by immunohistochemical staining methods.Results The results of prepulse inhibition test showed that significant differences of PP2,PP4 and PP8 results existed among control group,single-dose model group and double-dose model group (F=10.381,P=0.001,F=10.313,P=0.001,F=15.233,P=0.000).Compared with the control group,the two model groups showed significantly lower,the double-dose model group was lower than single-dose model group (P＜0.05).In passive avoidance test,there were significant differences of T1 and T2 results existed among control group,single-dose model group and double-dose model group (F=23.555,P=0.000,F=17.524,P=0.000).The T1 results of two model groups were significantly higher than control group,the double-dose model group was significantly higher than single-dose model group (P＜0.05) ; the T2 results of two model groups were lower than control group,the double-dose model group was lower than single-dose model group(P＜0.05).The results of passive avoidance test indicated that significant differences existed among control group,single-dose model group and double-dose model group in whole period of testing and total conditioned response rate(F=8.631,P=0.000,F=6.986,P=0.001),the two model groups were significantly lower than control group,double-dose model group was significantly lower than single-dose model group (P＜0.05).MBP results of two model groups were significantly lower than control group,two model groups had no significant difference (P＞ 0.05).Conclusion The adult offspring that were treated with Poly (I∶C) exit abnormal behavior and damaged white matter,and there is a correlation between the degree of abnormal behavior and drug dose.