Metabolomics studies on corticosterone-induced PC12 cells: A strategy for evaluating an in vitro depression model and revealing the metabolic regulation mechanism

There are three types of differentiated (un-, poorly- and well-differentiated) PC12 cells, which have been widely used as a model system for depression studies after the administration of corticosterone (CORT). In order to investigate the underlying metabolic profiles of CORT-induced PC12 cells and evaluate the suitable differentiated types of PC12 cells for use in depressive studies, proton nuclear magnetic resonance (1H NMR) metabolomics coupled with network analysis approaches were employed. The results showed that CORT induced metabolic alterations in PC12 cells. There were 8 and 13 common differential metabolites in intracellular and extracellular extracts, respectively, of the three types of differentiated PC12 cells in response to CORT treatment, and the perturbed metabolic pathways were involved in amino acid metabolism, glutathione metabolism, pyruvate metabolism and inositol phosphate metabolism. Eighteen protein targets of depression were identified from the five different metabolic pathways from metabolomics and network analysis among the three types of CORT-induced differentiated PC12 cells, and these proteins were all found in the pathways that were perturbed by CORT treatment of poorly-differentiated PC12 cells. These results may indicate that the metabolism of CORT-induced PC12 cells is similar to the pathogenesis of depression, and poorly-differentiated PC12 cells are the most suitable cells for depressive research among the distinct types of differentiated PC12 cells. Thus, an effective predicative strategy to evaluate the in vitro disease models could be referenced.