Abstract:
Schizophrenia is likely to be a consequence of serial alterations of a number of genes and proteins that, together with environmental factors, will lead to the establishment of the illness. Since proteomic analysis of post-mortem schizophrenia brains may lead to the identification of schizophrenia-related proteins that will ensure the comprehension of this pathogenesis as well as indicate potential biomarkers, we have collected post-mortem brain tissue from schizophrenia patients and control individuals of the dorsolateral prefrontal cortex (Brodmann’s Area 46), anterior temporal lobe (BA38), Wernicke’s Area (BA22p), mediodorsal thalamus and anterior cingulate cortex aiming to analyze their proteomes. We subjected those brain tissues to comparative proteome analysis using a shotgun mass spectrometry approach combining isoelectrofocusing and RP-HPLC prior MALDI-TOF/TOF powered by isotope coded protein labeling (ICPL) for proteome quantitation. Moreover, we used two-dimensional gel electrophoresis/mass spectrometry-based proteome analysis. We have found the most often alterations in energy metabolism, oligodendrocyte-function and myelinization, calcium homeostasis and cytoskeleton. Moreover, we have revealed the differential expression of a number of hypothetical or putative proteins, which might be interesting targets to further studies considering their underlie information. Several protein biomarker candidates such as myelin basic protein and myelin oligodendrocyte protein were evaluated and validated by western blot in some of the described brain regions as well as in cerebrospinal fluid from a separate set of samples. A number of glycolysis enzymes have been found differentially expressed in the analyzed brain regions, what have led us to quantify the levels of pyruvate and NADPH in thalamus, which indeed were found altered. The recurrent identification and validation of inter-related protein clusters, determined in different samples by different proteomic approaches not only strongly reinforces the putative involvement of certain pathways in SCZ, but also reveal new potential biomarkers and paves the way to the development of new therapeutic strategies in order to contribute for reducing the social and cognitive consequences of the disease.

Brief Biography of the Speaker:
Dr. Daniel Martins-de-Souza is an associate researcher in University of Cambridge at Cambridge Centre for Neuropsychiatric Research headed by Prof. Sabine Bahn working on proteomics of psychiatric disorders. Dr. Martins-de-Souza was a postdoc fellow in Max Planck Institute of Psychiatry in Munich, Germany, for 2 years and has obtained his Ph.D. in Biochemistry and Molecular Biology in State University of Campinas (UNICAMP) in Brazil, where he had started the investigations in the proteome analysis of schizophrenia brain tissue, aiming to find differentially expressed proteins which can lead to a better comprehension of this disorder as well as find potential biomarkers to help the clinical diagnosis. Dr. Martins-de-Souza has 32 published scientific articles and 3 book chapters.