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

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Auteurs principaux: Wen‐Wen Li, Rui Xiao, Xue‐Yi Chen, Jun‐Cai Pu, Jian‐Jun Chen, Hai‐Yang Wang, Lan‐Xiang Liu, Dan Li, Yang‐Dong Zhang, Wen‐Xia Li, Peng Xie
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Publié: Wiley 2025
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author Wen‐Wen Li
Rui Xiao
Xue‐Yi Chen
Jun‐Cai Pu
Jian‐Jun Chen
Hai‐Yang Wang
Lan‐Xiang Liu
Dan Li
Yang‐Dong Zhang
Wen‐Xia Li
Peng Xie
author_facet Wen‐Wen Li
Rui Xiao
Xue‐Yi Chen
Jun‐Cai Pu
Jian‐Jun Chen
Hai‐Yang Wang
Lan‐Xiang Liu
Dan Li
Yang‐Dong Zhang
Wen‐Xia Li
Peng Xie
Wen‐Wen Li
Rui Xiao
Xue‐Yi Chen
Jun‐Cai Pu
Jian‐Jun Chen
Hai‐Yang Wang
Lan‐Xiang Liu
Dan Li
Yang‐Dong Zhang
Wen‐Xia Li
Peng Xie
collection Wiley Open Access
contents Multi‐Omics Analysis Reveals Disturbances of Purine Metabolism and Glutamate Metabolism in the Hippocampus of Lipopolysaccharide‐Induced Mouse Model of Depression Wen‐Wen Li Rui Xiao Xue‐Yi Chen Jun‐Cai Pu Jian‐Jun Chen Hai‐Yang Wang Lan‐Xiang Liu Dan Li Yang‐Dong Zhang Wen‐Xia Li Peng Xie Brain and Behavior 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. 10.1002/brb3.70549 http://creativecommons.org/licenses/by/4.0/
doi_str_mv 10.1002/brb3.70549
format Artículo Open Access
id wiley_oa_10_1002_brb3_70549
institution Wiley Open Access
license_str_mv http://creativecommons.org/licenses/by/4.0/
publishDate 2025
publisher Wiley
record_format wiley_oa
spellingShingle Multi‐Omics Analysis Reveals Disturbances of Purine Metabolism and Glutamate Metabolism in the Hippocampus of Lipopolysaccharide‐Induced Mouse Model of Depression
Wen‐Wen Li
Rui Xiao
Xue‐Yi Chen
Jun‐Cai Pu
Jian‐Jun Chen
Hai‐Yang Wang
Lan‐Xiang Liu
Dan Li
Yang‐Dong Zhang
Wen‐Xia Li
Peng Xie
Brain and Behavior
Multi‐Omics Analysis Reveals Disturbances of Purine Metabolism and Glutamate Metabolism in the Hippocampus of Lipopolysaccharide‐Induced Mouse Model of Depression Wen‐Wen Li Rui Xiao Xue‐Yi Chen Jun‐Cai Pu Jian‐Jun Chen Hai‐Yang Wang Lan‐Xiang Liu Dan Li Yang‐Dong Zhang Wen‐Xia Li Peng Xie Brain and Behavior 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. 10.1002/brb3.70549 http://creativecommons.org/licenses/by/4.0/
title Multi‐Omics Analysis Reveals Disturbances of Purine Metabolism and Glutamate Metabolism in the Hippocampus of Lipopolysaccharide‐Induced Mouse Model of Depression
topic Brain and Behavior
url https://onlinelibrary.wiley.com/doi/10.1002/brb3.70549