Effects Of Before And After Birth Stimuli On Offsprings'Schizophrenia Like Behaviors And Its Mechanism

Objective:In this study,we want to investigate the schizophrenia-like behavior induced by"double stimuli" before and after the birth in mice and find out the mechanism of these two factors on the performance of the offspring.Besides we are curious about their possible interaction.Methods:Pregnant females dams were injected with Poly I:C(5mg/Kg)in caudal vein on GD17.Poly I:C activated maternal innate immunity and cytokines which affected fetus'neurodevelopment were produced.Poly I:C was the before-birth stimuli to pups.After birth,pups were treated as follows:(1)Maternal deprivation(n=168):Before weaning,1/2 pups were randomly selected to separate from their moms,while the others were not.(2)Enriched environment(n=171):After weaning,pups were randomly divided into two groups-dull environment(DE)group and enriched environment(EE)group.Pups in EE group were reared in cages with tools which were changed every week.DE group were reared in normal cages.(3)Social isolation(n=152):After weaning,half pups were isolated from their companies born in the same cage and reared alone in their cages,which are SI group;the others were reared with their companies and constituted SG group.On postnatal day 60,behavior test including open field,elevated plus maze,novel object recognition,social interaction,forced swimming test,tail suspension test,water maze were conducted.After behavior tests,all mice were killed,meanwhile hippocampus dissected and kept for further study.The expression of MBP was detected by western blot.Results:Poly I:C × maternal deprivation:for female pups,Poly I:C-treated ones entered more times into open arms in EPM explored more times around the novel object,spent more time in water maze to find the platform,compared with NS-treated ones.MPB in their hippocampus was reduced.Pups deprived from moms spent more time to find the platform in reversal learning.For male ones,pups treated with Poly I:C showed the same trend with female ones in EPM and reversal learning test.MBP in their hippocampus was reduced.The weight of mom-deprived ones was lower than mom-cared ones both in female and male pups.The two factors had no interactions.(2)Poly I:C x enriched environment:For female pups,Poly I:C-treated ones gained weight more faster.Their MBP expression was decreased in hippocampus.Pups reared in EE generated more movement distances in open field.Their immobility rate in FST was higher,they also spent more time in water maze to find the platform.For male ones,Poly I:C-treated ones showed the same trend in weight and MBP expression with female ones.Beyond that,Poly I:C-treated ones were more active in open field,entered more times into open arms in EPM and higher contact frequency in social interaction test;Pups reared in EE showed the same trend in water maze with female ones.(3)Poly I:C ×Social isolation:for female pups,Poly I:C-treated ones showed higher appearance frequency into open arms in EPM and immobility frequency in FST.They also spent more time to find the platform in reversal learning.Expression of MBP was reduced.Pups isolated from their companies showed no significant difference to gregarious ones.For male pups,Poly I:C-treated ones showed the same variation compared with NS-treated ones in EPM,FST and expression of MBP.Poly I:C decreased their weight growing.Besides,isolated ones showed lower frequency into open arms in EPM.Conclusions:(1)Poly I:C × Maternal deprivation:for female pups,moms,infection with Poly I:C during late pregnancy leads to a range of damage in pups including recognition ability,learning ability and reversal learning ability and myelin sheath in hippocampus,while anxiety is decreased.Maternal deprivation slows down their speed of weight gaining.For male ones,effects of Poly I:C are similar to female ones in learning ability,myelin sheath in hippocampus,anxiety behavior.So is the injury of myelin sheath in hippocampus.The two factors don't have antagonism.(2)Poly I:C × Enriched environment:for female pups,moms' infection with Poly I:C during late pregnancy leads to injury of myelin sheath in hippocampus and increase in spontaneous activity,learning ability.Depression tendency is reduced.For male pups,moms' infection withPoly I:C during pregnancy results in more spontaneous activity and injury of myelin sheath in hippocampus,but increases their social interaction.Learning ability is improved by EE.Poly I:C before birth and EE after birth have no synergism.(3)Social isolation:for female pups,moms' infection with Poly I:C during pregnancy decreases their depression tendency and reversal learning ability.Also myelin sheath was damaged in hippocampus.SI showed no influence on them.For male pups,moms' infection with Poly I:C during late pregnancy decreases their speed of gaining weight,as well as depression and social interaction.effect on myelin sheath is the same with female ones.SI increases pups' anxiety behavior.The two factors don't have antagonism.(4)Moms' infection with Poly I:C during late pregnancy and the three respective stimuli after birth don't have synergism or antagonism.