Effect Of Postnatal Environment On Schizophrenia-like Behaviors Induced By Early Prenatal Immune Challenge In Adult Mice Offspring

【Objective】To investigate the effect of postnatal environment such as positive or adverse environment on schizophrenia-like behaviors induced by maternal immune activation in the adulthood,to see if the postnatal environment can enhance or modify the risk of the prenatal immune activation.【Methods】The pregnant mice were injected with polynosinic-polycytidylic acid(Poly I:C)(5mg/kg),via intravenous route,at gestational day 9(GD 9).The offspring of these dams were given different treatments:(1)Enriched environment: after weaning on postnatal day 21(PND21),the offspring were randomly divided into two groups,including enriched environment group(EE)and dull environment group(DE).Different toys were put into the cages of EE groups and changed weekly.The DE groups were kept the normal housing environment only with sawdust.(2)Maternal deprivation: among PND1~21,the pups were removed from their dams to other cages at the same room temperature for 3 hours.The separate time was at the same time each day.Behavioral tests began from PND60 when the offspring were adult.Behavioral tests include prepulse inhibition(PPI),open field test,social interaction test,novel object/location recognition,tail suspension test,elevated plus-maze test,water maze test,et al.After behavioral tests,the offspring were killed and rapidly removed the hippocampus for further analysis and used western blot to analyze the expression of myelin basic protein(MBP)in the hippocampus.【Results】(1)Poly I:C×Enriched environment: The %PPI of offspring treated with early maternal immune activation of Poly I:C were significantly reduced when compared with control groups(both female and male offspring: p<0.05).Early maternal immune activation increased the moved distance and speed of the offspring compared with thecontrol groups in the open field test.(both female and male offspring: p<0.05).Enriched environment increased offspring’s social interaction time with strange mouse in the social interaction test(both female and male offspring: p<0.05).The male offspring of enriched environment groups spent less time in open arms in the elevated plus-maze test(p<0.05).In the tail suspension test,the male offspring of enriched environment groups kept more time immobility,while in the forced swimming test,they spent less time immobility(p<0.05).The female offspring treated with early maternal immune activation spent less time immobility(p<0.05).Enriched environment decreased the time of offspring to find the platform in water maze test(p<0.05)and the male offspring which received two treatments of Poly I:C and enriched environment spent less time in the probe test compared with other groups(p<0.05)。The offspring which received early maternal immune activation of Poly I:C showed lower expression of myelin basic protein in hippocampus than control groups(p<0.05).(2)Poly I:C×maternal deprivation: in the novel object recognition test,neither prenatal immune activation nor maternal deprivation could cause obvious changes of offspring’s behavior,while they had interaction effect.The offspring which received both the challenge of maternal immune activation and maternal deprivation spent more time in front of the novel object(p<0.05).The offspring treated with maternal deprivation spent more time with strange mouse compared to that of maternal care groups(p<0.05).In the elevated plus-maze test,the offspring received prenatal immune activation of Poly I:C spent more time in the open arms compared to the control groups(p<0.05).In the learning period of water maze test,the male offspring of maternal deprivation groups spent less time finding the platform(p<0.05).In the reverse learning period,either prenatal immune activation or maternal deprivation didn’t cause obvious changes on the time of finding the platform.Compared to other groups,the group of normal saline(NS)× maternal care(MC)found the platform much faster in the reverse learning period(p<0.05).The offspring which received early maternal immune activation of Poly I:C showed lower expression of myelin basic protein in hippocampus than that in control groups(p<0.05).【Conclusion】(1)Poly I:C×Enriched environment: our study demonstrated that the offspring received early maternal immune activation of Poly I:C showed deficits in sensory-motor gating and hyperactivity.Postnatal enriched environment could increase the abilities of social interaction and learning.The results of elevated plus-maze test,tail suspension test and forced swimming test showed that the postnatal enriched environment couldn’t modify the anxiety of the offspring.Postnatal enriched environment may modify the perseveration behavior of male offspring caused by early maternal immune activation of Poly I:C.(2)Poly I:C×Maternal deprivation: the results of novel object recognition test suggested that the effects of both early maternal immune activation and maternal deprivation may aggravate the perseveration behavior of the offspring.Early maternal immune activation of Poly I:C may decrease the offspring’s anxiety in elevated plus-maze test.The maternal deprivation may increase offspring’s aggressive behavior in social interaction test.The offspring received both prenatal immune activation and maternal deprivation may show enhanced ability of reverse learning.