| Objectives1. To investigate the activate state of microglia in vivo in mature offspring of prenatal infection rats model and to explore the role of activated microglia in the pathogenesis of schizophrenia.2. To explore the relationships among microglia activation, prenatal infection and behavior disorders.Methods1. The24female and3male specific pathogen free (SPF) colony Sprague-Dawley rats at the age of12to14weeks began breeding after2weeks of acclimatization to the new animal holding room. The breeding would be stopped until accomplished18pregnant rats.2. Pregnant rats were randomly divided into3groups. Each group had6rats. Drugs should be injection on gestation day nine (GD9). The three groups received5mg/kg Poly (I:C),10mg/kg Poly (I:C) and5mg/kg0.9%physiological saline respectively. Offspring of those groups served as model group, double does group and control group respectively.3. Behavioral test for three groups had been taken by spontaneous activity, prepulse Inhibition (PPI) and latent inhibition (LI) test (including active avoidance-conditioning task and passive avoidance-conditioning task).4. Randomly to select6successful model rats assessed by behavioral test in model group and double dose group respectively, as well as6control group rats. Micro PET/CT was performed to test the actived microglia in vivo by11C-(R)-PK11195.5. Expression of the actived microglia of the18selected rats was detected by immunohistochemistry technique.6. Data analysis was conducted using SPSS20.0for Windows. According to the different characteristics of different data, one-way ANOVA, multivariate analysis ANOVA, repeated measures ANOVA and correlation analysis were selected.Results1.18female rats were conceived successfully. The pregnant rats were injected smoothly.2. Significant differences were found in the three groups in spontaneous activity (P<0.001), PPI (PP2:P=0.008, PP4:P=0.001, PP8:P=0.002), the numbers of total conditioned response, the rate of total conditioned response during the whole period of active avoidance-conditioning task testing (P=0.005,.P=0.006) and the results of passive avoidance-conditioning task (P<0.001)3. Significant differences were found between model group and double dose group in PP4(P=0.047), PP8(P=0.028), T time of passive avoidance-conditioning task (P=0.013) and the rate of total conditioned response during the whole period of active avoidance-conditioning task testing (P=0.037).4. The micro PET/CT scan results showed that the activation of microglia in model group and double dose group increased in prefrontal and hippocampus, and the decay rate of model group and double dose group were lower than control group in prefrontal and hippocampus (P<0.001).5. The volume and numbers of microglia were increased, and the morphology was changed in prefrontal and hippocampus in the model group and double dose group. The optical density values of activated microglia in the model group and double dose group were lower than the control group in prefrontal and hippocampus (P=0.014, P=0.009).6. Correlation analysis showed that behavior results were correlated with the decay rate of PET and the optical density values of immunohistochemistry (P<0.05). the decay rate of PET was correlated with the optical density values of immunohistochemistry at the same brain area (P<0.05) Conclusions1. The activation of microglia was described in mature offspring of prenatal infection rat model in prefrontal and hippocampus, and the microglia activation was associated with schizophrenia-like behaviors. The microglia activation may play a role in the pathogenesis of schizophrenia.2. The dose of Poly (I:C) was positive correlated with PPI and latent inhibition. Because of the difference in the results of PET and immunohistochemistry, the relationship between the dose of Poly (I:C) and the activated state of microglia still needs further study. |
PDF Full Text Request