Dysmyelination by Oligodendrocyte-Specific Ablation of Ninj2 Contributes to Depressive-Like Behaviors.
Dysmyelination by Oligodendrocyte-Specific Ablation of Ninj2 Contributes to Depressive-Like Behaviors.
复制标题
少突胶质细胞特异性消融 Ninj2 导致髓鞘发育不良导致抑郁样行为。
DOI：
10.1002/advs.202103065
复制
发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Sun Y;Chen X;Ou Z;Wang Y;Chen W;Zhao T;Liu C;Chen Y
抑郁症是一种精神疾病，影响着世界上3亿多人。白色物质的缺失与抑郁症的发展有关。在这里，作者表明，少突胶质细胞特异性缺失神经损伤诱导蛋白2（Ninj 2）的小鼠表现出抑郁样行为。少突胶质细胞中Ninj 2的缺失抑制少突胶质细胞的发育和髓鞘形成，并损害神经元的结构和活性。Ninj 2通过直接结合少突胶质细胞中的TNFR 1竞争性抑制TNFα/TNFR 1信号通路。Ninj 2的缺失激活TNFα诱导的坏死性凋亡，并增加C-C基序趋化因子配体2（Ccl 2）的产生，这可能介导从少突胶质细胞到神经元的信号转导。通过给予Nec-1 s抑制坏死性凋亡，同时恢复少突胶质细胞发育，改善神经元兴奋性，并减少抑郁样行为。因此，本研究阐明了Ninj 2在抑郁症和髓鞘形成中的作用，揭示了少突胶质细胞和神经元之间的关系，并为抑郁症提供了潜在的治疗靶点。神经损伤诱导蛋白2（Ninj 2）的少突胶质细胞特异性缺失导致小鼠的抑郁样行为。Ninj 2的缺失通过诱导TNFα介导的坏死性凋亡抑制少突胶质细胞发育和髓鞘形成，损害神经元功能，并导致抑郁症。抑制坏死性凋亡可同步恢复少突胶质细胞发育并消除抑郁样行为。这些发现揭示了少突胶质细胞在抑郁症中的重要性。
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. Oligodendrocyte‐specific deletion of Nerve injury‐induced protein 2 （ Ninj2) leads to depressive‐like behaviors in mice. Loss of Ninj2 inhibits oligodendrocyte development and myelination by inducing TNFα‐mediated necroptosis, impairs neuron functions, and results in depression. Inhibition of necroptosis synchronously restores oligodendrocyte development and alleviates depressive‐like behaviors. The findings thus reveal the importance of oligodendrocytes in depression.
登录
查看更多内容
DOI：
10.1007/s43440-021-00280-w
发表时间：
2021-08
期刊：
Pharmacological reports : PR
影响因子：
--
作者：
Curzytek K;Leśkiewicz M
通讯作者：
Leśkiewicz M
影响因子：
10.5
作者：
Cole, James;Chaddock, Christopher A.;Fu, Cynthia H. Y.
通讯作者：
Fu, Cynthia H. Y.
影响因子：
4.7
作者：
Fan LW;Bhatt A;Tien LT;Zheng B;Simpson KL;Lin RC;Cai Z;Kumar P;Pang Y
通讯作者：
Pang Y
影响因子：
64.8
作者：
Aguilar-Valles, Argel;De Gregorio, Danilo;Sonenberg, Nahum
通讯作者：
Sonenberg, Nahum
影响因子：
14.8
作者：
Degterev, A;Huang, ZH;Yuan, JY
通讯作者：
Yuan, JY