Mice with Loss of Cystine-Glutamate Antiporter Display Behaviors Related to Schizophrenia

• Main Authors: Fu-Ju Lei, 雷馥如
• Other Authors: Chia-Hung Hsieh
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/3z3gxw

碩士 === 中國醫藥大學 === 臨床醫學研究所碩士班 === 102 === Cystine-glutamate antiporter can regulate the synthesis of glutathione and contribute to the concentration of extracellular glutamate. In schizophrenia pathology, glutamatergic transmission imbalance is an important issue for the molecular mechanism of schizophrenia. Base on cystine-glutamate antiporter play an important role in glutamatergic transmission, we thought that cystine-glutamate antiporter may cause schizophrenia pathology progress. According to this hypothesis, we use xCT knockout mice to test a series animal behavior tasks and investigating whether the mice display the abnormal behaviors and similar to the schizophrenia patients. Our results showed that mice loss of cystine-glutamate antiporter increased stereotypy impaired of PPI, decreased social interaction and nesting behavior. And these abnormal behaviors were related to schizophrenia patients. In addition, we took the frontal cortex and hippocampus from the control mice and xCT knockout mice to measure the concentration of glutamate and glutathione. However, there is no difference in glutathione between two groups. But the knockout mice were less than control group in glutamate concentration. We also use radiotracer to observe if the glutamate receptor, NMDAR, will be affect by cystine-glutamate antiporter dysfunction. In the PET image, indicated that NMDAR hypo-function in frontal cortex and hippocampus of xCT knockout mice. The results derived from our data, we considered that loss of xCT cause glutamatergic transmission hypo-function and induce schizophrenic symptoms is a useful animal model. We can use this model to explore system xc- dysfunction or hypo-function trigger by genetic, environment or other risks contribute to the schizophrenia pathologic progress and find the extension therapy