Open AccessDysmyelination by Oligodendrocyte‐Specific Ablation of Ninj2 Contributes to Depressive‐Like Behaviors
Author(s) -
Sun Yuxia,
Chen Xiang,
Ou Zhimin,
Wang Yue,
Chen Wenjing,
Zhao Tongjin,
Liu Changqin,
Chen Ying
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202103065
Subject(s) - oligodendrocyte , neuroscience , necroptosis , white matter , signal transduction , depression (economics) , microglia , microbiology and biotechnology , myelin , biology , medicine , psychology , inflammation , central nervous system , apoptosis , programmed cell death , magnetic resonance imaging , biochemistry , radiology , macroeconomics , economics
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 TNF α /TNFR1 signaling pathway by directly binding to TNFR1 in oligodendrocytes. Loss of Ninj2 activates TNF α ‐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.