Differential expression profiling of the synaptosome proteome in a rat model of antipsychotic resistance.

Baohu Ji, Zhao Zhang, Ming Zhang, Hui Zhu, Kejun Zhou, Jinglei Yang, Yang Li, Liya Sun, Guoyin Feng, Yujiong Wang, Lin He, Chunling Wan

Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.

Brain research 2009 Oct 27

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This study used a comparative proteomics approach to identify the effects of the antipsychotic drugs, Chlorpromazine (CPZ), Clozapine (CLZ), and Quetiapine (QTP) on the synaptosomal protein of the cerebral cortex of Sprague-Dawley (SD) rats. The multivariate statistical test partial least squares-discriminant analysis (PLS-DA) was applied to build the models for screening out the variable important plot (VIP). The PLS-DA models were able to distinguish each drug treatment group and the control group; more importantly, the univariate differentially expressed protein spots were capable of being verified by the VIP of the models. The interrelationships among the identified proteins were analyzed using Pearson's correlation analysis and pathway analysis. Through the synaptosome proteome experiments, we established that the energy production of the mitochondrial function and 'Glycolysis/Gluconeogenesis' were involved in the response to antipsychotic medications. Furthermore, the G protein-coupled signal transduction system was also inhibited by antipsychotic medications. The result of our study should contribute to the understanding of the effects of antipsychotic drugs on synaptic function.

Citation

Baohu Ji, Zhao Zhang, Ming Zhang, Hui Zhu, Kejun Zhou, Jinglei Yang, Yang Li, Liya Sun, Guoyin Feng, Yujiong Wang, Lin He, Chunling Wan. Differential expression profiling of the synaptosome proteome in a rat model of antipsychotic resistance. Brain research. 2009 Oct 27;1295:170-8