Stable Isotope-Resolved Metabolomics Studies on Corticosteroid-Induced PC12 Cells: A Strategy for Evaluating Glucose Catabolism in an in Vitro Model of Depression

Abstract

Depression is a common psychopathological state or mood disorder syndrome. The serious risks to human life and the inadequacy of the existing antidepressant drugs have driven us to understand the pathogenesis of depression from a new perspective. Our research group has found disturbances in glucose catabolism in both depression and nephrotic syndrome. What are the specific metabolic pathways and specificities of glucose catabolism disorders caused by depression? To address the above scientific questions, we creatively combined traditional metabolomics technology with stable isotope-resolved metabolomics to research the glucose catabolism of the corticosterone-induced PC12 cell damage model and the adriamycin-induced glomerular podocyte damage model. The results showed an increased flux of pyruvate metabolism in depression. The increased flux of pyruvate metabolism led to an activation of gluconeogenesis in depression. The disturbed upstream metabolism of succinate caused the tricarboxylic acid cycle (TCA cycle) to be blocked in depression. In addition, there were metabolic disturbances in the purine metabolism and pentose phosphate pathways in depression. Compared with nephrotic syndrome, pyruvate metabolism, the TCA cycle, and gluconeogenesis metabolism in depression were specific. The metabolic pathways researched above are likely to be important targets for the efficacy of antidepressants.

Study on Antidepressant Effect and Mechanism of Crocin Mediated by the mTOR Signaling Pathway

“…PC12 cells were derived from a pheochromocytoma cell line of rat adrenal medulla, and it is often used for in vitro studies of neurological diseases. CORT-treated PC12 cells are also often used to evaluate the effectiveness of antidepressant drugs [21][22][23][24]. We investigated the effects of crocin on the survival rate and neurons of CORT-induced PC12 cells.…”

Integrating Metabolomics and Network Analysis for Exploring the Mechanism Underlying the Antidepressant Activity of Paeoniflorin in Rats With CUMS-Induced Depression

“…Multiple studies have reported an association between the TCA cycle and depression. Some researchers believe that the TCA cycle is specific and blocked in depression ( Mishra et al, 2020 ; Ting et al, 2020 ; Tian et al, 2022 ). Mitochondrial dysfunction or changes in brain energy metabolism may be involved in the pathogenesis of depression ( Bansal and Kuhad 2016 ; Kolar et al, 2021 ).…”

Recent Progress in Mass Spectrometry-Based Metabolomics in Major Depressive Disorder Research

“…Acylcarnitine profiles also help to distinguish different phenotypic subtypes of MDD, such as core depression, anxious depression, and neurovegetative symptoms of melancholia [81]. Given that glycogen is the main energy source for most higher organisms, Qin's group used stable isotope-resolved metabolomics with a 13 C 6 -glucose tracer to reveal the blockage of the tricarboxylic acid cycle and abnormal activation of gluconeogenesis in rats with CUMS and in corticosteroid-induced PC12 cells [82][83][84][85][86].…”