Effect Of Ziprasidone On LPS Induced Microglia Activation

Background: Schizophrenia is a severe illness that affects approximately 1% of the world’s population. The etiology of schizophrenia is only partially understood. Neuro-inflammation mediated by active microglia may play a key role in the pathogenesis of schizophrenia. Although neither the cause of schizophrenia nor the mechanisms that mediate disease development are understood, accumulating evidence points to the significance of neuro-inflammation and immuno-genetics in the disease.Methods: 1. Build an animal model through intra-peritoneal injection of LPS(lipopolysaccharide) to stimulate systematic inflammation. 2. To detect the effect of Ziprasidone on the expression of NO through enzyme linked immuno-sorbent assay in vivio microglia. 3. To detect the effect of Ziprasidone on the expression of iNOS protein treated with different drug concentration in vivo and vitro through western blot. 4. To detect the expression of oxidized protein treated with different Ziprasidone concentration in vivo and vitro through Oxyblot. 5. To detect the effect of Ziprasidone on the expression of iNOS mRNA through RT-PCR.Main results: In vivo:1. To build an animal model through intraperitoneal injection of LPS to stimulate systematic inflammation; 2. LPS induces microglia-derived iNOS expression in the corpus striatum. 3. LPS induced microglia-derived iNOS expression in the corpus striatum is inhibited by Ziprasidone, but not by Sulpiride.4. Ziprasidone can inhibited LPS-induced protein oxidation in the corpus striatum。5. Ziprasidone can inhibited the expression of mRNAs for iNOS in the corpus striatum. 6. LPS and Ziprasidone have no effect on the expression of gp91 phox.In vitro: 1.Ziprasidone can inhibited LPS-induced NO production in BV2 cells. 2. Ziprasidone can inhibited LPS induced microglia-derived iNOS expression. 3. Ziprasidone can inhibited LPS-induced protein oxidation in BV-2 cells.4. Ziprasidone can inhibited the expression of mRNAs for iNOS in the corpus striatum。5. LPS and Ziprasidone have no effect on the expression of gp91 phox in BV-2 cells’ cuture.Conclusion: Our study on the mechanism of the effect of atypical antipsychotic to microglia activation may help us to identify the mechanism of drug action, guide the clinical drug use, and which also help us to understand the mechanism of schizophrenia. All those can provide us new idea to develop new drug, to provide the theoretical basis for clinical treatment of schizophrenia, and finally find the gold key of science to sure the schizophrenia.