An 1H NMR and UPLC–MS-based plasma metabonomic study to investigate the biochemical changes in chronic unpredictable mild stress model of depression

Abstract

Depression is a common and highly debilitating psychiatric illness. However, the pathophysiology of depression is not fully understood. In this study SpragueDawley rats were exposed to chronic unpredictable mild stress (CUMS) to induce depression. A metabonomic study on plasma of CUMS-induced depressive rats was performed to research the pathologic mechanism of depression by using 1 H nuclear magnetic resonance (NMR) spectroscopy and ultra performance liquid chromatography coupled to mass spectrometry (UPLC-MS). Clear separations between depressive rats and control rats were observed by principal component analysis (PCA) based on the data obtained using both analytical techniques and 18 significantly changed metabolites were identified as potential biomarkers of depression. Depressive rats were characterized by altered levels of plasma lysophosphatidylcholines, amino acids, cholic acid, choline, lactate, glycoproteins, glucose, ketone bodies, nucleosides and gut microflora metabolites, which were related to multiple perturbed metabolic pathways and contributed to the elucidation of the complex mechanism of depression. To the best of our knowledge, this is the first plasma metabonomic study on CUMS-induced depressive rats by using two complementary analytical technologies. Our results showed that metabonomic approach offers a useful tool to identify depression-specific biomarkers and provide new insights into the pathophysiology of depression.

Metabonomic identification of the effects of the Zhimu-Baihe saponins on a chronic unpredictable mild stress-induced rat model of depression

“…However, an increased glutamic acid content can also induce neurotoxicity [32]. Glutamic acid and glutamine can interconvert mutually in vivo, which is very important for maintaining their balance [33]. Our results showed that the glutamine levels were significantly decreased in the CUMS group, indicating an imbalanced glutamic acid-glutamine metabolism and lower conversion ratio of glutamic acid to glutamine, which may thereby affect the glutamic acid content in the rats.…”

1H-NMR-Based Metabonomic Studies on the Anti-Depressant Effect of Genipin in the Chronic Unpredictable Mild Stress Rat Model

“…At the same time, the increase in serum lactate, the end-product of glycolysis, indicates the inhibition of glycolysis and the inhibition of gluconeogenesis. This may be related to anaerobic cell respiration, an energy metabolism process that indicates low metabolism efficiency [29]. The increase in serum alanine after the CUMS procedure is likely the result of protein catabolism under stress, with a possible contribution from generally reduced levels of gluconeogenesis [30].…”

NMR- and LC–MS/MS-based urine metabolomic investigation of the subacute effects of hexabromocyclododecane in mice

“…Diseases have also been linked to the amino acid in metabolomics. A chronic unpredictable mild stress model of depression had found the changes of valine and glutamine (Zheng et al 2011). More importantly, some amino acids have been used as biomarkers to diagnose and predict diseases.…”