Multi-Omics Analysis Reveals Disturbances of Purine Metabolism and Glutamate Metabolism in the Hippocampus of Lipopolysaccharide-Induced Mouse Model of Depression

Abstract

Background

Depression is a global health concern characterized by high incidence, disability, and disease burden. Neuroimmunity, through the secretion of inflammatory mediators and mediation of neuroinflammation, plays a significant role in depression's pathogenesis. However, the underlying molecular mechanisms remain poorly understood.

Methods

In this pioneering study, we employed a comprehensive multi-omics approach, integrating 2-DE proteomics, liquid chromatography mass spectrometry-based metabolomics, and real-time polymerase chain reaction (PCR) array, to investigate the hippocampal molecular profiles of lipopolysaccharide (LPS)-induced immune inflammation-related depression. This innovative approach aimed to explore the potential pathogenesis of depression by systematically integrating data across multiple molecular layers.

Results

Compared to the control group, we identified 81 differential proteins, 44 differential metabolites, and 4 differential mRNAs in LPS-treated mice. Integrated analysis of these multidimensional data revealed that purine metabolism and glutamate metabolism are the most significantly altered molecular pathways in LPS-induced depression. Additionally, we constructed the corresponding compound-reaction-enzyme-gene regulatory network.

Conclusion

This study suggests that purine metabolism and glutamate metabolism may be the underlying mechanisms by which neuroinflammation regulates depression-like behaviors. Our findings confirm the important role of immune inflammation in depression and provide a new clue for the diagnosis and treatment of this disorder. Notably, the multi-omics approach employed in this study represents a pioneering effort in the field, providing unprecedented insights into the molecular mechanisms underlying depression.