O potencial da rotulação metabólica de 15N para a pesquisa de esquizofrenia

Abstract

Psychiatric research is in need of non-hypothesis driven approaches to unravel the neurobiological underpinnings and identify molecular biomarkers for psychiatric disorders. Proteomics methodologies constitute a state-of-the-art toolbox for biomarker discovery in psychiatric research. Here we present the principle of in vivo 15 N metabolic labeling for quantitative proteomics experiments and applications of this method in animal models of psychiatric phenotypes, with a particular focus on schizophrenia. Additionally we explore the potential of 15 N metabolic labeling in different experimental set-ups as well as methodological considerations of 15 N metabolic labeling-based quantification studies.Filiou MD / Rev Psiq Clín. 2013;40(1):51-2 Keywords: Schizophrenia, quantitative proteomics, 15 N metabolic labeling, biomarker, G72. ResumoPesquisas em psiquiatria ainda necessitam de estudos não dirigidos por hipóteses para revelar fundamentos neurobiológicos e biomarcadores moleculares para distúrbios psiquiátricos. Metodologias proteômicas disponibilizam uma série de ferramentas para esses fins. Apresentamos o princípio de rotulação metabólica utilizando 15 N para proteômica quantitativa e suas aplicações em modelos animais de fenótipos psiquiátricos com um foco particular em esquizofrenia. Exploramos o potencial de rotulação metabólica por 15 N em diferentes tipos de experimentos, bem como suas considerações metodológicas. The need for quantitative proteomics in schizophrenia researchIn the last years, the development of holistic approaches such as genomics, transcriptomics, proteomics and metabolomics has given rise to quantitative, non-hypothesis driven research applications. In this regard, populations of genes, proteins or metabolites of two states (e.g. disease vs. control) can be compared to identify expression level differences relevant to the observed phenotypic alterations. As the proteome of an organism can reflect phenotypic changes at the molecular level, proteomics constitutes a valuable tool to investigate the underlying mechanisms involved in psychiatric disorders.Research in schizophrenia suffers from a lack of molecular correlates for the observed behavioral alterations and disease symptoms. Molecular biomarkers for schizophrenia can aid the assessment of predisposition risk, the accurate subcategorization of patients, the monitoring of disease progression and the discovery of novel therapeutic targets. To this end, quantitative proteomics has the potential to provide sensitive molecular biomarker information and therefore offer valuable insights for schizophrenia prognosis, diagnosis and treatment. N metabolic labelingA number of quantitative proteomics approaches are available and applicable to schizophrenia research 1 . Among them, in vivo 15 N metabolic labeling holds great potential for studies in animal models as well as in patient cohorts. The principle of 15 N metabolic labeling is based on the introduction of the stable nitrogen isotope 15 N in an organism through either a 15 N-...