Integrating transcriptomics and metabolomics to analyze the protective effect of taurine on doxorubicin-induced depression

Abstract

Objective: Doxorubicin (Dox) is an effective anticancer drug with potent antitumor activity. However, the application of Dox is limited by its adverse reaction, including depression. Taurine can alleviate depression induced by multiple factors. It is still unclear if and how taurine improves DOX-induced depression. Methods: Mice were randomly divided into three groups (n = 4): (1) the control group, (2) the DOX group, and (3) the DOX+Taurine group. The open field test (OFT), elevated plus maze test (EPM), and forced swim test (FST) were first performed to assess the effects of Dox and taurine on the behavior of mice. Next, a combined transcriptomic and metabolomic analysis was performed to analyze the possible anti-depressive effect of taurine. Results: Taurine pretreatment increased the total travel time of mice in OFT and the time spent in the open arm in the EMP test and reduced the immobility time in FST. In addition, 201 differential genes and 51 differential metabolites were detected in the DOX+Taurine group compared to the DOX group. Furthermore, differential genes and differential metabolites were detected to be jointly involved in 21 pathways, which may be closely related to the antidepressant effect of taurine. Conclusions: Taurine alleviated DOX-induced depressive behavior. The various pathways detected in this study such as serotonergic synapse, and the inflammatory mediator regulation of TRP channels may be key regulatory pathways related to depression and antidepressant effects.