| BackgroundThe pathogenesis of schizophrenia is complicated,and the expression of inflam matory factors and brain derived neurotrophic factor(BDNF)in peripheral blood of patients is different from those of normal individuals.Prenatal exposure to a virus analogue poly inosine acid cytidine acid(Polyinosine-polycytidylic acid PolyI: C)will leads to a series of mental disorders in adult offspring rats and alterations of a variety of neurotransmitters.ObjectiveTo explore the changes of behavioral,central brain derived neurotrophic factor(BDNF)expressions as well as the levels of serum inflammatory factors in adolesce nt and adult schizophrenia rats derived from the offsprings of the pregnant rats pois oned by PolyI: C.MethodPolyI:C was injected into a cohort of female rats during pregnancy to prepare the model of schizophrenic rats.Behavioral measurements of spontaneous activity,anxiety,learning and memory were performed in the adolescent rats(6 weeks)and adult rats(8 weeks),and the behavioral measurements were also performed 30 days after resperidone treatment in the model group and the control group was randoml y selected with equal proportions in the adult rats.The expressions of interleukin-6(IL-6)and tumor necrosis factorα(TNF-α)in the blood as well as the brain BDN F expressions were detected by ELISA and qPCR,respectively.Results 1.The serum levels of IL-6 and TNF-α in pregnant female rats were significantly i ncreased 3 hours after PolyI:C injection,with a statistically significant difference(p< 0.05).2.Behavioral measurement: the model group showed an increased locomotor activi ty in adolescent rats of the expected schizophrenia,and Y maze showed a decrease d exploratory learning ability with increased initial arm residence time and decrease d novel arm residence time(p < 0.05).However,the time spent in and the frequen cy of entering the open arm of EPM and the distance traveled in the central area were not significantly changed in adolescent rats(p > 0.05);In adulthood,there wa s a decreased locomotor activity,and the reduced learning and memory capacity in the Y maze test(p < 0.05).And,the entry frequency and the time in open arms of the EPM were decreased,and the distance traveled by adult rats in the central a rea was reduced,reflecting an increased anxiety(p < 0.05).3.The analysis of serum expression of TNF-α and IL-6 proteins was done by ELI SA.The serum levels of TNF-α and IL-6 in female and male rats in the model gr oup were not significantly different from those in the control group during adolesce nce(p > 0.05),while the serum levels of TNF-α and IL-6 in the model group wer e significantly higher than those in the control group in the adult period(p < 0.05).4.In the qPCR test,the expressions of prefrontal BDNF mRNA in the model group were lower than those of the control groups in adulthood or adolescence(p < 0.05).After resperidone treatment in adult rats,there was a significant difference betw een the treated and the untreated model groups(p < 0.05),without gender differenc e(p > 0.05).There was no significant difference in the mRNA expression of BDN F in the hippocampus(p > 0.05).The mRNA expression of BDNF in the striatum showed no significant in adolecent schizophrenia rats(p > 0.05),but was significa ntly lower in the adult male schizophrenia group compared with the normal male c ontrol group(p < 0.05).There were no significant differences in BDNF mRNA exp ression observed in femal rats(p > 0.05).There was a significant difference in BD NF mRNA expression between the resperidone treated schizophrenia group and the untreated schizophrenia group(p < 0.05).5.The protein expressions of BDNF in the prefrontal lobe of both the adolescent a nd adult schizophrenia rats were significantly lower than those of the control norma l groups(p < 0.05).There was no significant difference in the expression of stria BDNF between the adolescent schizophrenia group and the control group(p > 0.05).However,the expression of stria BDNF in adult schizophrenia rats was significa ntly lower than that of the normal control group(p < 0.05).There was a significan t difference in BDNF expression between the resperidone treated schizophrenia grou p and the untreated schizophrenia group(p < 0.05).ConclusionIn adolescent and adult schizophrenia rats induced by PolyI:C,there were decr eased BDNF gene and protein expressions in the prefrontal cortex and the striatum,in addition,in adult schizophrenia rats,the increased levels of sera IL-6 and TNF-α seem to be associated with increased anxiety-like behavior. |
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