Integrative Analysis of Long Non-coding RNAs, Messenger RNAs, and MicroRNAs Indicates the Neurodevelopmental Dysfunction in the Hippocampus of Gut Microbiota-Dysbiosis Mice
Major depressive disorder is caused by gene–environment interactions and the gut microbiota plays a pivotal role in the development of depression. However, the underlying mechanisms remain elusive. Herein, the differentially expressed hippocampal long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs...
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| Format: | Article |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2021.745437/full |
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| author | Lanxiang Liu Lanxiang Liu Lanxiang Liu Haiyang Wang Haiyang Wang Xueyi Chen Yangdong Zhang Wenxia Li Xuechen Rao Xuechen Rao Yiyun Liu Libo Zhao Juncai Pu Juncai Pu Siwen Gui Deyu Yang Liang Fang Peng Xie Peng Xie Peng Xie Peng Xie |
| author_facet | Lanxiang Liu Lanxiang Liu Lanxiang Liu Haiyang Wang Haiyang Wang Xueyi Chen Yangdong Zhang Wenxia Li Xuechen Rao Xuechen Rao Yiyun Liu Libo Zhao Juncai Pu Juncai Pu Siwen Gui Deyu Yang Liang Fang Peng Xie Peng Xie Peng Xie Peng Xie |
| author_sort | Lanxiang Liu |
| collection | DOAJ |
| description | Major depressive disorder is caused by gene–environment interactions and the gut microbiota plays a pivotal role in the development of depression. However, the underlying mechanisms remain elusive. Herein, the differentially expressed hippocampal long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), and microRNAs (miRNAs) between mice inoculated with gut microbiota from major depressive disorder patients or healthy controls were detected, to identify the effects of gut microbiota-dysbiosis on gene regulation patterns at the transcriptome level, and in further to explore the microbial-regulated pathological mechanisms of depression. As a result, 200 mRNAs, 358 lncRNAs, and 4 miRNAs were differentially expressed between the two groups. Functional analysis of these differential mRNAs indicated dysregulated inflammatory response to be the primary pathological change. Intersecting these differential mRNAs with targets of differentially expressed miRNAs identified 47 intersected mRNAs, which were mainly related to neurodevelopment. Additionally, a microbial-regulated lncRNA–miRNA–mRNA network based on RNA–RNA interactions was constructed. Subsequently, according to the competitive endogenous RNAs (ceRNA) hypothesis and the biological functions of these intersected genes, two neurodevelopmental ceRNA sub-networks implicating in depression were identified, one including two lncRNAs (4930417H01Rik and AI480526), one miRNA (mmu-miR-883b-3p) and two mRNAs (Adcy1 and Nr4a2), and the other including six lncRNAs (5930412G12Rik, 6430628N08Rik, A530013C23Rik, A930007I19Rik, Gm15489, and Gm16251), one miRNA (mmu-miR-377-3p) and three mRNAs (Six4, Stx16, and Ube3a), and these molecules could be recognized as potential genetic and epigenetic biomarkers in microbial-associated depression. This study provides new understanding of the pathogenesis of depression induced by gut microbiota-dysbiosis and may act as a theoretical basis for the development of gut microbiota-based antidepressants. |
| first_indexed | 2024-12-20T07:25:39Z |
| format | Article |
| id | doaj.art-9913a0f11f8e40d393752df418e0b350 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-20T07:25:39Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-9913a0f11f8e40d393752df418e0b3502022-12-21T19:48:33ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-01-011410.3389/fnmol.2021.745437745437Integrative Analysis of Long Non-coding RNAs, Messenger RNAs, and MicroRNAs Indicates the Neurodevelopmental Dysfunction in the Hippocampus of Gut Microbiota-Dysbiosis MiceLanxiang Liu0Lanxiang Liu1Lanxiang Liu2Haiyang Wang3Haiyang Wang4Xueyi Chen5Yangdong Zhang6Wenxia Li7Xuechen Rao8Xuechen Rao9Yiyun Liu10Libo Zhao11Juncai Pu12Juncai Pu13Siwen Gui14Deyu Yang15Liang Fang16Peng Xie17Peng Xie18Peng Xie19Peng Xie20Department of Neurology, Yongchuan 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, ChinaDepartment of Neurology, 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, ChinaCollege of Stomatology and Affiliated Stomatological 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, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaCollege of Biomedical Engineering, Chongqing Medical University, Chongqing, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Neurology, Yongchuan 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, ChinaDepartment of Neurology, 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, ChinaDepartment of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Neurology, Yongchuan 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, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaCollege of Stomatology and Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing, ChinaMajor depressive disorder is caused by gene–environment interactions and the gut microbiota plays a pivotal role in the development of depression. However, the underlying mechanisms remain elusive. Herein, the differentially expressed hippocampal long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), and microRNAs (miRNAs) between mice inoculated with gut microbiota from major depressive disorder patients or healthy controls were detected, to identify the effects of gut microbiota-dysbiosis on gene regulation patterns at the transcriptome level, and in further to explore the microbial-regulated pathological mechanisms of depression. As a result, 200 mRNAs, 358 lncRNAs, and 4 miRNAs were differentially expressed between the two groups. Functional analysis of these differential mRNAs indicated dysregulated inflammatory response to be the primary pathological change. Intersecting these differential mRNAs with targets of differentially expressed miRNAs identified 47 intersected mRNAs, which were mainly related to neurodevelopment. Additionally, a microbial-regulated lncRNA–miRNA–mRNA network based on RNA–RNA interactions was constructed. Subsequently, according to the competitive endogenous RNAs (ceRNA) hypothesis and the biological functions of these intersected genes, two neurodevelopmental ceRNA sub-networks implicating in depression were identified, one including two lncRNAs (4930417H01Rik and AI480526), one miRNA (mmu-miR-883b-3p) and two mRNAs (Adcy1 and Nr4a2), and the other including six lncRNAs (5930412G12Rik, 6430628N08Rik, A530013C23Rik, A930007I19Rik, Gm15489, and Gm16251), one miRNA (mmu-miR-377-3p) and three mRNAs (Six4, Stx16, and Ube3a), and these molecules could be recognized as potential genetic and epigenetic biomarkers in microbial-associated depression. This study provides new understanding of the pathogenesis of depression induced by gut microbiota-dysbiosis and may act as a theoretical basis for the development of gut microbiota-based antidepressants.https://www.frontiersin.org/articles/10.3389/fnmol.2021.745437/fulldepressiongut microbiotalncRNAsmRNAsmiRNAs |
| spellingShingle | Lanxiang Liu Lanxiang Liu Lanxiang Liu Haiyang Wang Haiyang Wang Xueyi Chen Yangdong Zhang Wenxia Li Xuechen Rao Xuechen Rao Yiyun Liu Libo Zhao Juncai Pu Juncai Pu Siwen Gui Deyu Yang Liang Fang Peng Xie Peng Xie Peng Xie Peng Xie Integrative Analysis of Long Non-coding RNAs, Messenger RNAs, and MicroRNAs Indicates the Neurodevelopmental Dysfunction in the Hippocampus of Gut Microbiota-Dysbiosis Mice Frontiers in Molecular Neuroscience depression gut microbiota lncRNAs mRNAs miRNAs |
| title | Integrative Analysis of Long Non-coding RNAs, Messenger RNAs, and MicroRNAs Indicates the Neurodevelopmental Dysfunction in the Hippocampus of Gut Microbiota-Dysbiosis Mice |
| title_full | Integrative Analysis of Long Non-coding RNAs, Messenger RNAs, and MicroRNAs Indicates the Neurodevelopmental Dysfunction in the Hippocampus of Gut Microbiota-Dysbiosis Mice |
| title_fullStr | Integrative Analysis of Long Non-coding RNAs, Messenger RNAs, and MicroRNAs Indicates the Neurodevelopmental Dysfunction in the Hippocampus of Gut Microbiota-Dysbiosis Mice |
| title_full_unstemmed | Integrative Analysis of Long Non-coding RNAs, Messenger RNAs, and MicroRNAs Indicates the Neurodevelopmental Dysfunction in the Hippocampus of Gut Microbiota-Dysbiosis Mice |
| title_short | Integrative Analysis of Long Non-coding RNAs, Messenger RNAs, and MicroRNAs Indicates the Neurodevelopmental Dysfunction in the Hippocampus of Gut Microbiota-Dysbiosis Mice |
| title_sort | integrative analysis of long non coding rnas messenger rnas and micrornas indicates the neurodevelopmental dysfunction in the hippocampus of gut microbiota dysbiosis mice |
| topic | depression gut microbiota lncRNAs mRNAs miRNAs |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2021.745437/full |
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