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 Sprague-Dawley 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 1H 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.