Nrf2 regulates the arginase 1+ microglia phenotype through the initiation of TREM2 transcription, ameliorating depression-like behavior in mice
Abstract The expression of the triggering receptor on myeloid cell-2 (TREM2) knockdown in microglia from the lateral habenula (LHb) reportedly induces depression-like behaviors in mice. However, the key molecular mechanism that mediates major depressive disorder (MDD) pathogenesis remains elusive. W...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-10-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-022-02227-y |
| _version_ | 1797984711579009024 |
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| author | Lujuan He Yi Zheng Lixuan Huang Jingyi Ye Yinyi Ye Hanyue Luo Xi Chen Wei Yao Jiaxu Chen Ji-chun Zhang |
| author_facet | Lujuan He Yi Zheng Lixuan Huang Jingyi Ye Yinyi Ye Hanyue Luo Xi Chen Wei Yao Jiaxu Chen Ji-chun Zhang |
| author_sort | Lujuan He |
| collection | DOAJ |
| description | Abstract The expression of the triggering receptor on myeloid cell-2 (TREM2) knockdown in microglia from the lateral habenula (LHb) reportedly induces depression-like behaviors in mice. However, the key molecular mechanism that mediates major depressive disorder (MDD) pathogenesis remains elusive. We herein show that Nrf2 regulates TREM2 transcription and effects TREM2 mRNA and protein expression. The activation of Nrf2 by sulforaphane (Nrf2 activator) increases the microglial arginase 1+ phenotype by initiating TREM2 transcription in the medial prefrontal cortex (mPFC) and ameliorates depression-like behavior in CSDS mice. The knockout of Nrf2 decreases TREM2 and the microglial arginase 1+ phenotype in the mPFC of Nrf2 KO mice with depression-like behavior. Downregulating TREM2 expression decreases the microglial arginase 1+ phenotype in the mPFC, resulting in depression-like behavior in SFN-treated CSDS mice. Finally, the knockout of Nrf2 and downregulation of TREM2 expression decreases the microglial arginase 1+ phenotype in the mPFC of Nrf2 KO mice and SFN-treated CSDS mice were associated with the brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling pathway. These data indicate that alterations in the interaction between Nrf2 and TREM2 may play a role in the pathophysiology of depression-like behavior in mice. |
| first_indexed | 2024-04-11T07:06:06Z |
| format | Article |
| id | doaj.art-d173eb1bb6a940e083ff62faa61bab7a |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-11T07:06:06Z |
| publishDate | 2022-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-d173eb1bb6a940e083ff62faa61bab7a2022-12-22T04:38:23ZengNature Publishing GroupTranslational Psychiatry2158-31882022-10-0112111410.1038/s41398-022-02227-yNrf2 regulates the arginase 1+ microglia phenotype through the initiation of TREM2 transcription, ameliorating depression-like behavior in miceLujuan He0Yi Zheng1Lixuan Huang2Jingyi Ye3Yinyi Ye4Hanyue Luo5Xi Chen6Wei Yao7Jiaxu Chen8Ji-chun Zhang9Department of Physiology, School of Medicine, Jinan UniversityDepartment of Physiology, School of Medicine, Jinan UniversityDepartment of Physiology, School of Medicine, Jinan UniversityDepartment of Physiology, School of Medicine, Jinan UniversityDepartment of Physiology, School of Medicine, Jinan UniversityDepartment of Physiology, School of Medicine, Jinan UniversityDepartment of Anesthesiology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityGuangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan UniversityGuangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan UniversityDepartment of Physiology, School of Medicine, Jinan UniversityAbstract The expression of the triggering receptor on myeloid cell-2 (TREM2) knockdown in microglia from the lateral habenula (LHb) reportedly induces depression-like behaviors in mice. However, the key molecular mechanism that mediates major depressive disorder (MDD) pathogenesis remains elusive. We herein show that Nrf2 regulates TREM2 transcription and effects TREM2 mRNA and protein expression. The activation of Nrf2 by sulforaphane (Nrf2 activator) increases the microglial arginase 1+ phenotype by initiating TREM2 transcription in the medial prefrontal cortex (mPFC) and ameliorates depression-like behavior in CSDS mice. The knockout of Nrf2 decreases TREM2 and the microglial arginase 1+ phenotype in the mPFC of Nrf2 KO mice with depression-like behavior. Downregulating TREM2 expression decreases the microglial arginase 1+ phenotype in the mPFC, resulting in depression-like behavior in SFN-treated CSDS mice. Finally, the knockout of Nrf2 and downregulation of TREM2 expression decreases the microglial arginase 1+ phenotype in the mPFC of Nrf2 KO mice and SFN-treated CSDS mice were associated with the brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling pathway. These data indicate that alterations in the interaction between Nrf2 and TREM2 may play a role in the pathophysiology of depression-like behavior in mice.https://doi.org/10.1038/s41398-022-02227-y |
| spellingShingle | Lujuan He Yi Zheng Lixuan Huang Jingyi Ye Yinyi Ye Hanyue Luo Xi Chen Wei Yao Jiaxu Chen Ji-chun Zhang Nrf2 regulates the arginase 1+ microglia phenotype through the initiation of TREM2 transcription, ameliorating depression-like behavior in mice Translational Psychiatry |
| title | Nrf2 regulates the arginase 1+ microglia phenotype through the initiation of TREM2 transcription, ameliorating depression-like behavior in mice |
| title_full | Nrf2 regulates the arginase 1+ microglia phenotype through the initiation of TREM2 transcription, ameliorating depression-like behavior in mice |
| title_fullStr | Nrf2 regulates the arginase 1+ microglia phenotype through the initiation of TREM2 transcription, ameliorating depression-like behavior in mice |
| title_full_unstemmed | Nrf2 regulates the arginase 1+ microglia phenotype through the initiation of TREM2 transcription, ameliorating depression-like behavior in mice |
| title_short | Nrf2 regulates the arginase 1+ microglia phenotype through the initiation of TREM2 transcription, ameliorating depression-like behavior in mice |
| title_sort | nrf2 regulates the arginase 1 microglia phenotype through the initiation of trem2 transcription ameliorating depression like behavior in mice |
| url | https://doi.org/10.1038/s41398-022-02227-y |
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