Iron overload in the motor cortex induces neuronal ferroptosis following spinal cord injury.
Iron overload in the motor cortex induces neuronal ferroptosis following spinal cord injury.
复制标题
DOI：
10.1016/j.redox.2021.101984
复制
发表时间：
2021-07
期刊：
影响因子：
11.4
通讯作者：
Hou J
中科院分区：
文献类型：
--
作者：
Feng Z;Min L;Chen H;Deng W;Tan M;Liu H;Hou J
运动神经元死亡被认为会导致脊髓损伤 (SCI) 后原发性运动皮层萎缩，这与 SCI 患者的运动恢复较差有关。然而，运动神经元死亡的确切机制仍然难以捉摸。在这里，我们证明了 SCI 患者和大鼠运动皮层中的铁沉积显着增加，这引发了脂质活性氧 (ROS) 的积累，最终导致运动神经元铁死亡。而铁螯合剂、ROS抑制剂和铁死亡抑制剂可减少铁过载引起的运动神经元死亡并促进运动功能恢复。此外，我们发现 SCI 后运动皮层中激活的小胶质细胞分泌丰富的一氧化氮 (NO)，它调节细胞铁稳态相关蛋白，从而诱导运动神经元铁过载。因此，我们得出结论，SCI 后小胶质细胞活化诱导运动皮层铁过载，引发运动神经元铁死亡并阻碍运动功能恢复。这些发现可能为 SCI 提供新的治疗策略。 SCI 会导致运动皮层铁过载。 SCI后铁过载会诱导脂质过氧化，从而引发神经元铁死亡。 SCI 后，M1 中激活的小胶质细胞会分泌多余的 NO 来扰乱铁代谢。
Motor neuron death is supposed to result in primary motor cortex atrophy after spinal cord injury (SCI), which is relevant to poorer motor recovery for patients with SCI. However, the exact mechanisms of motor neuron death remain elusive. Here, we demonstrated that iron deposition in the motor cortex was significantly increased in both SCI patients and rats, which triggered the accumulation of lipid reactive oxygen species (ROS) and resulted in motor neuronal ferroptosis ultimately. While iron chelator, ROS inhibitor and ferroptosis inhibitor reduced iron overload-induced motor neuron death and promoted motor functional recovery. Further, we found that activated microglia in the motor cortex following SCI secreted abundant nitric oxide (NO), which regulated cellular iron homeostasis-related proteins to induce iron overload in motor neurons. Thus, we conclude that microglial activation induced iron overload in the motor cortex after SCI triggered motor neuronal ferroptosis and impeded motor functional recovery. These findings might provide novel therapeutic strategies for SCI. SCI induces iron overload in the motor cortex. Iron overload after SCI induces lipid peroxidation, thus triggers neuronal ferroptosis. Activated microglia in M1 secrete superfluous NO to disturb iron metabolism after SCI.
登录
查看更多内容
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
3.3
作者：
Hou, J-M.;Sun, T. -S.;Li, H-T.
通讯作者：
Li, H-T.
影响因子：
5.3
作者：
Ayton, Scott;Lei, Peng;Bush, Ashley I.
通讯作者：
Bush, Ashley I.
影响因子：
3
作者：
Carlson, GD;Gorden, CD;LaManna, JC
通讯作者：
LaManna, JC
人类脊髓损伤早期的大脑感觉运动系统萎缩
影响因子：
3.3
作者：
Hou, J. -M.;Yan, R. -B.;Sun, T. -S.
通讯作者：
Sun, T. -S.