Evaluation the Therapeutic Effect of Adipose-Derived Mesenchymal Stem Cells on Chronic Mild Stress by Activating PEBP1-GPX4 Axis in Ferroptosis Using qRT-PCR, Fluorescence Microscope and Iron Determination Analysis

Abstract

About 50% of depressive patients failed to respond to the treatment, mainly because of insufficient knowledge about the pathogenesis of depression. The current study’s objectives were to look into the potential role of ferroptosis in the etiology of depression in the mice model of chronic mild stress (CMS) and investigate the effects of adipose-derived mesenchymal stem cells (ADSCs) on PEBP1-GPX4 axis controlled ferroptosis in mice. We grouped the male C57BL/6 mice randomly as follows: normal control (NC), CMS, and CMS+ADSCs. The second two groups’ animals were exposed to CMS for a total of six weeks. From the fourth week of modeling to the sixth week, cell therapy was given once a week. SPT, TST, FST, and NSFT behavior assessments were used to evaluate the depression-like behavior brought on by CMS. We selected the ferroptosis-related parameters, including the expression of GPX4, FTH1, ACSL4, and COX2. The amount of iron was determined in the hippocampus of the model organism by using the iron assay kit. By measuring the PEBP1 and ERK1/2 levels, as well as evaluating the expression of GFAP and IBA1, we assessed the biological function of astrocytes and microglia in mice hippocampus. It was found that six weeks after modeling in the CMS+ADSCs group, the mice’s depression-like behavior induced by CMS had significantly improved. We found a significantly changed level of genes, including GPX4, ACSL4, FTH1, COX2, ERK1/2, GFAP, PEBP1 and IBA1. Also, we found the differentiated level of total and ferric iron in our model mice. All these findings demonstrated that ADSCs had a therapeutic effect on CMS-induced depression-like behavior, probably by activating the PEBP1-GPX4 axis in ferroptosis. This anti-depression role of ADSCs may be associated with the activation of the PEBP1-GPX4 axis in ferroptosis, implying that regulation of ferroptosis is a crucial therapeutic target for depression.