| First Author | Sun Y | Year | 2022 |
| Journal | Adv Sci (Weinh) | Volume | 9 |
| Issue | 3 | Pages | e2103065 |
| PubMed ID | 34787377 | Mgi Jnum | J:324127 |
| Mgi Id | MGI:7266798 | Doi | 10.1002/advs.202103065 |
| Citation | Sun Y, et al. (2022) Dysmyelination by Oligodendrocyte-Specific Ablation of Ninj2 Contributes to Depressive-Like Behaviors. Adv Sci (Weinh) 9(3):e2103065 |
| abstractText | 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 TNFalpha/TNFR1 signaling pathway by directly binding to TNFR1 in oligodendrocytes. Loss of Ninj2 activates TNFalpha-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. |
