CLOZAPINE AFFECTS THE INFLAMMATORY IMMUNE RESPONSE IN THE BRAINS OF SCHIZOPHRENIC RATS BY REGULATING Β - CATENIN/APC/GSK-3Β GENE

Xiu Li, Huirong Chen, Qiaoan Zhang^*

Department of Laboratory, Hanchuan People's Hospital, Hanchuan 431600, Hubei Province, China

Objective: To investigate the effect of clozapine on the inflammatory immune response in the brains of schizophrenic rats by regulating β-Catenin, GSK-3 β and the APC gene. 

Methods: Twenty-one SD rats were randomly divided into a control group, a model group (using MK-801 to establish a model for schizophrenia and intraperitoneal injections of equal volume of normal saline) and a clozapine group (establishing a model for schizophrenia and treatment with 1mg/kg clozapine). The peripheral blood T cell subsets CD3 +, CD4 +, CD8a +, IgG, IgA, IgM, IL-2, IL-6, IL-1 β, TNF-α, Bcl-2, β-Catenin mRNA, and APC were compared in each group. The expression of mRNA and GSK-3 β mRNA and the number of IL-1 β, TNF-α and Bcl-2 positive cells in the rats’ brains were also assessed. 

Results: The levels of CD3 +, CD4 + and CD8a + in the model group were significantly higher than in the control group (P<0.05). The levels of CD3 +, CD4 + and CD8a + in the clozapine group were significantly lower than in the model group (P<0.05). The levels of IgG, IgA and IgM in the model group were significantly higher than in the control group (P<0.05). The levels of IgG, IgA and IgM in the clozapine group were significantly lower than in the model group (P<0.05). The water level of IL-2 and IL-6 in the model group was significantly higher than in the control group, and the level of TNF-α was significantly lower than in the control group (P<0.05). The water level of IL-2 and IL-6 in the clozapine group was significantly higher than in the model group, and the level of TNF-α in the clozapine group was significantly higher than in the model group (P<0.05). In the brain tissues of rats of the model group, the number of TNF-α and IL-1 β positive cells was significantly higher than in those of the control group, and the number of Bcl-2 positive cells was significantly lower than in those of the control group (P<0.05). In the brain tissues of rats of the clozapine group, the number of TNF-α positive cells was significantly lower than in those of the model group, and the number of Bcl-2 positive cells was significantly higher than in those of the model group (P<0.05). The expression of β-Catenin mRNA in the model group was significantly higher than in the control group, and GSK-3β and APC mRNA were significantly lower than that in the control group (P<0.05). The expression of β-Catenin mRNA in the clozapine group was significantly lower than in the model group, while GSK-3β and APC mRNA were significantly higher than in the model group (P<0.05). 

Conclusion: Clozapine can inhibit the inflammatory immune response in the brains of schizophrenic rats by regulating the gene expression of β-Catenin, APC and GSK-3β.