A systems biology approach compared protein changes in anterior prefrontal cortex tissue from four glutamatergic rodent models of schizophrenia and from human post-mortem schizophrenia patients. Liquid chromatography-tandem mass spectrometry proteomic profiling identified five functional domains of the disease, including "development and differentiation," represented across all rodent models. Kernel-based machine learning quantified that the chronic phencyclidine (PCP) model most closely resembled schizophrenia brain changes for four of these domains. The authors argue this methodology helps evaluate which rodent model best recapitulates neuropathological features of schizophrenia, supporting efforts to link functional behavioral dimensions with distinct biological processes.
Chronic administration of phencyclidine to rats produces schizophrenia-like symptoms and alters proteins and metabolites in the frontal cortex that overlap with changes seen in the prefrontal cortex of people with schizophrenia. Proteomic profiling identified alterations in glutamate-mediated calcium signaling, mitochondrial function, and cytoskeletal remodeling; metabonomic profiling revealed changes in glutamate, glutamine, glycine, pyruvate, and the calcium regulator taurine. The similarities, though not identical, indicate the rat model captures only some molecular features of the disease. The findings suggest that multiple models may be needed to better translate to human schizophrenia and aid drug discovery.