Co and Contra-Regulation of Glycosylated Proteins in Three Distinct Regions of Schizophrenics Brain

Background: Schizophrenia, a multifactorial disorder exhibits diverse neuropathological aberrations with altered protein expression and post translational modifications as surfacing evidence that may also contribute to its pathophysiology. Objective: To investigate the integrated picture of molecular changes and potential alterations in expression of specific glycosylated proteins in different brain regions compared to physiologically normal brains. We aimed to provide more holistic view of three brain regions; and their dynamic cross-talk providing insights into the underlying molecular mechanisms associated with schizophrenia. Methods: Present study entails, differential proteomic analysis of autopsied brain regions of schizophrenic; substantia nigra, cortex, and hippocampus (n=7 each), by using sodium dodecyl sulphate polyacrylamide gel electrophoresis coupled with immunoblot and DIG (digoxigenin) labelling followed by ESI-QTOF MS analysis for validation. Results: We have detected fourteen glycosylated protein components with altered expression among the three studied brain regions, with two contra and a coregulated protein. The 50KDa (Glial fibrillary acidic protein, GFAP) and 84KDa (mitochondrial inner membrane protein) are contra-regulated between substantia nigra and cortex, while T-complex protein 1 subunit zeta of 58KDa is coregulated between substantia nigra and hippocampus. Besides co and contra regulated proteins, remaining proteins with significantly altered glycosylation intensity in the specific brain regions give evidence of their explicit regional function. Additionally, nine proteins commonly appeared nonglycosylated in the three studied brain regions. Conclusion: The characterization of expressed glycoproteins globally and their co and contra regulation could be due to strong regional association of disease associated pathways probably as a result of their modulatory roles following post-translational modification.