QUANTITATIVE SUBCELLULAR PROTEOMICS OF THE ORBITOFRONTAL CORTEX OF SCHIZOPHRENIA PATIENTS

Schizophrenia is a chronic disease characterized by the impairment of mental functions with a marked social dysfunction. A proteomic approach using iTRAQ labeling and selected reaction monitoring, applied to the characterization of mitochondria (MIT), crude nuclear fraction (NUC) and cytoplasm (CYT), can allow the observation of dynamic changes in cell compartments providing valuable insights concerning schizophrenia physiopathology. Mass spectrometry analyses of the orbitofrontal cortex from 12 schizophrenia patients and 8 healthy controls identified 655 protein groups in MIT fraction, 1500 in NUC and 1591 in CYT. We found 166 groups of proteins dysregulated among all enriched cellular fractions. Through the quantitative proteomic analysis, we detect as the main biological pathways those related to calcium and glutamate imbalance, cell signaling disruption of CREB activation, axon guidance and proteins involved in the activation of NF-kB signaling along with the increase of complement proteins C3. Based on our data analysis, we suggest the activation of NF-kB as a possible pathway that links the deregulation of glutamate, calcium, apoptosis and the activation of the immune system in schizophrenia patients