Dysmyelination by Oligodendrocyte‐Specific Ablation of Ninj2 Contributes to Depressive‐Like Behaviors
Abstract Depression is a mental disorder affecting more than 300 million people in the world. Abnormalities in white matter are associated with the development of depression. Here, the authors show that mice with oligodendrocyte‐specific deletion of Nerve injury‐induced protein 2 （Ninj2) exhibit dep...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202103065 |
| _version_ | 1818952523443077120 |
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| author | Yuxia Sun Xiang Chen Zhimin Ou Yue Wang Wenjing Chen Tongjin Zhao Changqin Liu Ying Chen |
| author_facet | Yuxia Sun Xiang Chen Zhimin Ou Yue Wang Wenjing Chen Tongjin Zhao Changqin Liu Ying Chen |
| author_sort | Yuxia Sun |
| collection | DOAJ |
| description | Abstract Depression is a mental disorder affecting more than 300 million people in the world. Abnormalities in white matter are associated with the development of depression. Here, the authors show that mice with oligodendrocyte‐specific deletion of Nerve injury‐induced protein 2 （Ninj2) exhibit depressive‐like behaviors. Loss of Ninj2 in oligodendrocytes inhibits oligodendrocyte development and myelination, and impairs neuronal structure and activities. Ninj2 competitively inhibits TNFα/TNFR1 signaling pathway by directly binding to TNFR1 in oligodendrocytes. Loss of Ninj2 activates TNFα‐induced necroptosis, and increases C‐C Motif Chemokine Ligand 2 (Ccl2) production, which might mediate the signal transduction from oligodendrocyte to neurons. Inhibition of necroptosis by Nec‐1s administration synchronously restores oligodendrocyte development, improves neuronal excitability, and alleviates depressive‐like behaviors. This study thus illustrates the role of Ninj2 in the development of depression and myelination, reveals the relationship between oligodendrocytes and neurons, and provides a potential therapeutic target for depression. |
| first_indexed | 2024-12-20T09:51:44Z |
| format | Article |
| id | doaj.art-2b01ce855fbf43f58355f406eaf6fbca |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-20T09:51:44Z |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-2b01ce855fbf43f58355f406eaf6fbca2022-12-21T19:44:34ZengWileyAdvanced Science2198-38442022-01-0193n/an/a10.1002/advs.202103065Dysmyelination by Oligodendrocyte‐Specific Ablation of Ninj2 Contributes to Depressive‐Like BehaviorsYuxia Sun0Xiang Chen1Zhimin Ou2Yue Wang3Wenjing Chen4Tongjin Zhao5Changqin Liu6Ying Chen7State Key Laboratory of Cellular Stress Biology School of Life Sciences Xiamen University Xiamen Fujian 361005 ChinaState Key Laboratory of Cellular Stress Biology School of Life Sciences Xiamen University Xiamen Fujian 361005 ChinaState Key Laboratory of Cellular Stress Biology School of Life Sciences Xiamen University Xiamen Fujian 361005 ChinaState Key Laboratory of Cellular Stress Biology School of Life Sciences Xiamen University Xiamen Fujian 361005 ChinaState Key Laboratory of Cellular Stress Biology School of Life Sciences Xiamen University Xiamen Fujian 361005 ChinaShanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative Biology Zhongshan Hospital Fudan University Shanghai 200438 ChinaDepartment of Endocrinology and Diabetes The First Affiliated Hospital of Xiamen University Fujian Province Key Laboratory of Diabetes Translational Medicine Xiamen Fujian 361101 ChinaState Key Laboratory of Cellular Stress Biology School of Life Sciences Xiamen University Xiamen Fujian 361005 ChinaAbstract Depression is a mental disorder affecting more than 300 million people in the world. Abnormalities in white matter are associated with the development of depression. Here, the authors show that mice with oligodendrocyte‐specific deletion of Nerve injury‐induced protein 2 （Ninj2) exhibit depressive‐like behaviors. Loss of Ninj2 in oligodendrocytes inhibits oligodendrocyte development and myelination, and impairs neuronal structure and activities. Ninj2 competitively inhibits TNFα/TNFR1 signaling pathway by directly binding to TNFR1 in oligodendrocytes. Loss of Ninj2 activates TNFα‐induced necroptosis, and increases C‐C Motif Chemokine Ligand 2 (Ccl2) production, which might mediate the signal transduction from oligodendrocyte to neurons. Inhibition of necroptosis by Nec‐1s administration synchronously restores oligodendrocyte development, improves neuronal excitability, and alleviates depressive‐like behaviors. This study thus illustrates the role of Ninj2 in the development of depression and myelination, reveals the relationship between oligodendrocytes and neurons, and provides a potential therapeutic target for depression.https://doi.org/10.1002/advs.202103065depressionnecroptosisNinj2oligodendrocytes |
| spellingShingle | Yuxia Sun Xiang Chen Zhimin Ou Yue Wang Wenjing Chen Tongjin Zhao Changqin Liu Ying Chen Dysmyelination by Oligodendrocyte‐Specific Ablation of Ninj2 Contributes to Depressive‐Like Behaviors Advanced Science depression necroptosis Ninj2 oligodendrocytes |
| title | Dysmyelination by Oligodendrocyte‐Specific Ablation of Ninj2 Contributes to Depressive‐Like Behaviors |
| title_full | Dysmyelination by Oligodendrocyte‐Specific Ablation of Ninj2 Contributes to Depressive‐Like Behaviors |
| title_fullStr | Dysmyelination by Oligodendrocyte‐Specific Ablation of Ninj2 Contributes to Depressive‐Like Behaviors |
| title_full_unstemmed | Dysmyelination by Oligodendrocyte‐Specific Ablation of Ninj2 Contributes to Depressive‐Like Behaviors |
| title_short | Dysmyelination by Oligodendrocyte‐Specific Ablation of Ninj2 Contributes to Depressive‐Like Behaviors |
| title_sort | dysmyelination by oligodendrocyte specific ablation of ninj2 contributes to depressive like behaviors |
| topic | depression necroptosis Ninj2 oligodendrocytes |
| url | https://doi.org/10.1002/advs.202103065 |
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