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Abnormalities in white matter are associated with the development of depression. Here, the authors show that mice with oligodendrocyte\u2010specific deletion of\n                    <jats:italic>Nerve injury\u2010induced protein 2 \uff08Ninj2)<\/jats:italic>\n                    exhibit depressive\u2010like behaviors. Loss of\n                    <jats:italic>Ninj2<\/jats:italic>\n                    in oligodendrocytes inhibits oligodendrocyte development and myelination, and impairs neuronal structure and activities. Ninj2 competitively inhibits TNF\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \/TNFR1 signaling pathway by directly binding to TNFR1 in oligodendrocytes. Loss of\n                    <jats:italic>Ninj2<\/jats:italic>\n                    activates TNF\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010induced necroptosis, and increases C\u2010C Motif Chemokine Ligand 2 (Ccl2) production, which might mediate the signal transduction from oligodendrocyte to neurons. Inhibition of necroptosis by Nec\u20101s administration synchronously restores oligodendrocyte development, improves neuronal excitability, and alleviates depressive\u2010like 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.\n                  <\/jats:p>","DOI":"10.1002\/advs.202103065","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T07:41:48Z","timestamp":1637134908000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Dysmyelination by Oligodendrocyte\u2010Specific Ablation of\n                    <i>Ninj2<\/i>\n                    Contributes to Depressive\u2010Like Behaviors"],"prefix":"10.1002","volume":"9","author":[{"given":"Yuxia","family":"Sun","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology School of Life Sciences Xiamen University  Xiamen Fujian 361005 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology School of Life Sciences Xiamen University  Xiamen Fujian 361005 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimin","family":"Ou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology School of Life Sciences Xiamen University  Xiamen Fujian 361005 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology School of Life Sciences Xiamen University  Xiamen Fujian 361005 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology School of Life Sciences Xiamen University  Xiamen Fujian 361005 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongjin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative Biology Zhongshan Hospital Fudan University  Shanghai 200438 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changqin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes The First Affiliated Hospital of Xiamen University Fujian Province Key Laboratory of Diabetes Translational Medicine  Xiamen Fujian 361101 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5675-1928","authenticated-orcid":false,"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology School of Life Sciences Xiamen University  Xiamen Fujian 361005 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,17]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-00930-0"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31948-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2016.08.016"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/874387"},{"key":"e_1_2_9_3_3","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-016-9645-z"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.2.871"},{"key":"e_1_2_9_5_1","first-page":"36","volume":"178","author":"Nave K. 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