Effects Of Maternal Immune Activation On The Age-related Changes Of Dopamine Receptors And Behaviors In Rat Progeny

BackgroundSchizophrenia is a destructive and disabling neuropsychiatric disease whose etiology and pathogenesis are still unclear.There is increasing evidence that its pathogenesis may be related to neurodevelopmental abnormalities.Neurotransmitter disorders have an important influence in the development of schizophrenia.ObjectivesThe early pregnancy infection model was prepared by virus analogs,and the behavioral and molecular expression of the offspring at different developmental stages were analyzed to explore the behavior of offspring caused by infection during pregnancy and the characteristics of dopamine receptors at different developmental nodes.Methods1.Pathogenic breeding(9 weeks old)was performed on pathogen-free(SPF grade)SD rats.2.Rats were injected with Poly I: C at a dose of 10 mg/kg on the 9th day of pregnancy.Some animals were tested for inflammatory factors IL-6,IL-1β and TNF-α to analyze the inflammatory activation status of pregnant rats.3.After the mice were weaned,the behaviors were analyzed in the puberty and adulthood by testing the behaviors of the pups,the elevated plus maze,the Y maze,the passive avoidance experiment,and the PPI.After the behavioral test,the hippocampus and frontal lobe brain tissues were taken.The molecular levels of dopamine receptor and tyrosine hydroplane were detected by real-time quantitative PCR.The protein levels of dopamine receptor and tyrosine hydroplane were detectedby western blot.The expression and distribution of tyrosine hydroplane were detected by radiochemistry.Results1.Compared with the control group,the expression levels of inflammatory cytokines IL-6(P = 0.0004),IL-1β(P = 0.0147)and TNF-α(P= 0.0002)were significantly increased in the plasma of pregnant groups of Poly I: C group.2.Adolescent behavioral results: Compared with the control group,the total distance of the movement in the Poly I:C group in the open field experiment increased significantly(P=0.0269);In the prepulse inhibition experiment,the inhibition rate was reduced by 80 decibels(P = 0.0454).Adult behavioral results:Compared with the control group,the movement distance of the Poly I:C group in the open field experimental center area was significantly reduced(P=0.0006);the Poly I:C group entered the elevated cross maze.The number of open arms(P=0.0001)and time was significantly reduced(P=0.0349);The number of new arms in the Poly I:C group in the Y-maze experiment(P=0.004)was significantly reduced;The time of finding the target hole in the Barnes labyrinth was significantly increased in the Poly I:C group(P=0.0346);the Poly I:C group was 75 dB in the prepulse inhibition experiment.The inhibition rates of =0.0001),80dB(P=0.0002),and 85dB(P=0.0007)were all reduced.3.RT-PCR results showed that compared with the control group,the expression level of D1 R gene in Poly I:C group increased significantly in hippocampus and frontal lobe during lactation,and the expression level of D2 R gene was significantly increased in hippocampus and frontal lobe during lactation and puberty increased.TH gene expression levels increased in the hippocampus and frontal lobes during lactation and puberty,and decreased in adult hippocampus and frontal lobe.4.Western blot results showed that compared with the control group,the D1 R protein expression level in the Poly I:C group increased in the frontal lobe of the lactation period,and the D2 R protein expression level increased significantly in the hippocampus and frontal lobes during the lactation and puberty,adulthood.Therewas no change in protein levels;TH protein expression levels increased in the hippocampus and frontal lobes during lactation and adolescence,while in the adult hippocampus and frontal lobe decreased.5.Immunofluorescence results showed that compared with the control group,the number of TH positive cells in the hippocampus and frontal lobes of the Poly I:C group was significantly increased during the lactation and puberty(P<0.05);the number of TH positive cells in adulthood was significant Reduced(P > 0.05).ConclusionsMaternal immune-activated progeny rats have disorders of dopamine receptor expression,and exhibit progressive schizophrenia-like behavior,not only verifying that the Poly I:C model is an ideal model for simulating schizophrenia,but also for schizophrenia.Preventive treatment provides scientific evidence and new ideas for diagnosis and treatment.