Maternal Immune Activation Leads To NMDA Receptor Disorder In Offspring Rats And Relationship With Abnormal Behavior

BackgroundMaternal immune activation during pregnancy is considered a high-risk factor for neuropsychiatric disorders,including schizophrenia.Exposure to Poly I:C during pregnancy will result in impaired learning ability in offspring adult rats,a series of psychotic behaviors such as cognitive disorders,and abnormalities in central glutamatergic excitatory neurotransmitters.ObjectivesThrough the injection of Poly I:C on the 9th day of pregnancy,the behavior and molecular detection of its offspring at different time periods were used to explore the offspring behavior and the age-dependent changes of NMDA receptors during pregnancy,and to analyze the relationship between the two.MethodsPathogenic breeding(9 weeks old)was performed on pathogen-free(SPF grade)SD rats.10 mg/kg Poly I:C and an equal volume of 0.9% saline were injected into the tail of GD9.After 3 hours,3 animals were randomly selected as quality control.The behaviors of the pups and the molecular levels of NMDA receptor and PSD95 in hippocampus and frontal lobe were detected in adolescence and adulthood,respectively.Results1.The expression level of inflammatory factors in the plasma of pregnant mice in the model group was significantly higher than that in the controls.2.In open field experiment,the adolescent model group had a greater distance in the central region than the control group,and the adult model group had a smaller distance in the central region than the control group.In the elevated experiment,the percentage of time in the adult model group compared with the control group was significantly lower than that in the control group,and there was no difference in puberty.In the Y maze experiment,the time and frequency of entering the new arm in the adult model group were significantly reduced,and there was no difference in puberty.In the Barnes labyrinth experiment,the time of finding safe holes on the first day,the second day,and the fourth day of the adult model rats increased,and there was no difference in puberty.In the pre-pulse inhibition experiment,the inhibition rate of all the decibels in the adult model group was reduced,and there was no difference in puberty.3.The progeny of schizophrenia model rats during pregnancy decreased the gene level of NMDA receptor in hippocampus during lactation,and there was no significant difference in the gene level of PSD95,and the NMDAR2 A and NMDAR2 B in prefrontal lobe decreased.The gene levels of NMDAR1,NMDAR2 A,NMDAR2B and PSD95 in hippocampus of adolescent model rats did not change,and only NMDAR2 A in prefrontal leaves increased.Adult model rats showed a significant increase in the gene level of hippocampal NMDAR2 A,while the prefrontal NMDAR2 B and PSD95 increased.The results of immunoblotting showed that the model rats in the lactation period showed a decrease in the level of NMDA receptors in the hippocampus and frontal lobe.Adolescent model rats showed no difference in protein levels between NMDA receptor and PSD95 in hippocampus and frontal lobe.The protein level of NMDAR2 A in hippocampus of adult model rats was significantly higher than that of the control group,and the protein levels of NMDA receptor and PSD95 in the prefrontal cortex increased.4.The results of immunofluorescence showed that the expression level of NMDAR1 in the hippocampal CA1 region of the offspring of MIA was significantly lower than that of the control group.The expression level of NMDAR1 in the frontal lobe of MIA adult was significantly higher than that in the control group.5.The protein expression level of NMDAR2 B in the prefrontal cortex of adult offspring was negatively correlated with the number of open arms in the elevated test;the time of entering the new arm in the forehead NMDAR2 A and Y maze test was negatively correlated.ConclusionsPregnancy infected offspring showed progressive schizophrenia-like behavior in adulthood,and the expression and distribution of NMDA receptors in hippocampus and frontal lobe were significantly disordered,and these phenomena appeared before behavioral abnormalities.Adolescence or early developmental stages may be a more important period of prevention and treatment of schizophrenia.