Effects of postnatal enriched environment on schizophrenia-related behaviors induced by early prenatal polynosinic-polycytidylic acid immune challenge in adult mice offspring

Abstract

Objective To investigate if the positive postnatal environment could modify the schizophrenia-related behaviors caused by early maternal immune activation, and the interaction of this two pre-and postnatal factors. Methods The pregnant mice were randomly divided into experimental and control groups.The experimental groups were injected with polynosinic-polycytidylic acid (Poly I∶C) (5mg/kg), via intravenous route, at gestational day 9.The control groups were injected with the same volume of normal saline (NS) at the same gestational day.All offspring were housed in groups of littermates until postnatal day (PND) 21 when they were weaned.Between PND22-PND60, offspring were divided into dull or enriched environment (DE or EE) groups by sex and treatment.Different toys were put into the cages of enriched environment group every week, such as running wheels, climbing materials, swings and rollers.The dull environment (DE) groups were kept the normal housing environment only with sawdust.At PND60, behavioral tests were conducted, such as prepulse inhibition (PPI), open field test, novel object/location recognition, social interaction test, as well as water maze test, were conducted to evaluate the performance of all offspring.After behavioral tests, all offspring were killed and the hippocampus were dissected.The western blot was used to analyze the expression of myelin basic protein in the hippocampus. Results (1) The percentage of PPI with early maternal immune activation of Poly I∶C were significantly reduced when compared with control groups(female offspring: F=28.12, P<0.001; male offspring: F=14.76, P<0.01), suggesting the schizophrenia-like behavioral deficit in the offspring induced by early prenatal Poly I∶C challenge.(2) In open field test, early maternal immune activation increased the moved distance and speed of the offspring compared with the control groups (female offspring: distances, F=5.10, P<0.05, speed: F=5.19, P<0.05; male offspring: distances: F=6.76, P<0.05, velocity: F=6.85, P<0.05, vs each corresponding control). (3) Enriched environment increased the social interaction time of offspring with strange mouse in the social interaction test (female offspring: EE group(101.30±6.83)s, DE group(76.50±5.59)s, F=9.41, P<0.01; male offspring: EE group(98.52±6.82)s, DE group(75.82±3.95)s, F=7.95, P<0.01). (4) Enriched environment decreased the time for offspring to find the platform in water maze test (P<0.05). (5)The expression of myelin basic protein in hippocampus in offspring which received early maternal immune activation by Poly I∶C was lower than that in the control groups (P<0.05). Conclusion The postnatal enriched environment increased the social interaction and the learning abilities of the offspring with early maternal immune activation by Poly I∶C in water maze, and even more improved the perseveration behavior of the offspring induced by the early maternal immune activation. Key words: Schizophrenia-related behavior; Polynosinic-polycytidylic acid; Maternal immune activation; Enriched environment; Animal model