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 under...
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Wiley
2025-05-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.70549 |
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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 |
| author_sort | Wen‐Wen Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d5a387aa1da440c29bced74b4cd82231 |
| institution | OA Journals |
| issn | 2162-3279 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj-art-d5a387aa1da440c29bced74b4cd822312025-08-20T02:29:19ZengWileyBrain and Behavior2162-32792025-05-01155n/an/a10.1002/brb3.70549Multi‐Omics Analysis Reveals Disturbances of Purine Metabolism and Glutamate Metabolism in the Hippocampus of Lipopolysaccharide‐Induced Mouse Model of DepressionWen‐Wen Li0Rui Xiao1Xue‐Yi Chen2Jun‐Cai Pu3Jian‐Jun Chen4Hai‐Yang Wang5Lan‐Xiang Liu6Dan Li7Yang‐Dong Zhang8Wen‐Xia Li9Peng Xie10Faculty of Basic Medicine, Department of Pathology Chongqing Medical University Chongqing ChinaFaculty of Basic Medicine, Department of Pathology Chongqing Medical University Chongqing ChinaFaculty of Basic Medicine, Department of Pathology Chongqing Medical University Chongqing ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases The First Affiliated Hospital of Chongqing Medical University Chongqing ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases The First Affiliated Hospital of Chongqing Medical University Chongqing ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases The First Affiliated Hospital of Chongqing Medical University Chongqing ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases The First Affiliated Hospital of Chongqing Medical University Chongqing ChinaFaculty of Basic Medicine, Department of Pathology Chongqing Medical University Chongqing ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases The First Affiliated Hospital of Chongqing Medical University Chongqing ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases The First Affiliated Hospital of Chongqing Medical University Chongqing ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases The First Affiliated Hospital of Chongqing Medical University Chongqing ChinaABSTRACT 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.https://doi.org/10.1002/brb3.70549depressionproteomicsmetabolomicsmulti‐omics analysis |
| spellingShingle | 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 Multi‐Omics Analysis Reveals Disturbances of Purine Metabolism and Glutamate Metabolism in the Hippocampus of Lipopolysaccharide‐Induced Mouse Model of Depression Brain and Behavior depression proteomics metabolomics multi‐omics analysis |
| title | Multi‐Omics Analysis Reveals Disturbances of Purine Metabolism and Glutamate Metabolism in the Hippocampus of Lipopolysaccharide‐Induced Mouse Model of Depression |
| title_full | Multi‐Omics Analysis Reveals Disturbances of Purine Metabolism and Glutamate Metabolism in the Hippocampus of Lipopolysaccharide‐Induced Mouse Model of Depression |
| title_fullStr | Multi‐Omics Analysis Reveals Disturbances of Purine Metabolism and Glutamate Metabolism in the Hippocampus of Lipopolysaccharide‐Induced Mouse Model of Depression |
| title_full_unstemmed | Multi‐Omics Analysis Reveals Disturbances of Purine Metabolism and Glutamate Metabolism in the Hippocampus of Lipopolysaccharide‐Induced Mouse Model of Depression |
| title_short | Multi‐Omics Analysis Reveals Disturbances of Purine Metabolism and Glutamate Metabolism in the Hippocampus of Lipopolysaccharide‐Induced Mouse Model of Depression |
| title_sort | multi omics analysis reveals disturbances of purine metabolism and glutamate metabolism in the hippocampus of lipopolysaccharide induced mouse model of depression |
| topic | depression proteomics metabolomics multi‐omics analysis |
| url | https://doi.org/10.1002/brb3.70549 |
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