Exposure to X-rays Causes Depression-like Behaviors in Mice via HMGB1-mediated Pyroptosis
Exposure to X-rays Causes Depression-like Behaviors in Mice via HMGB1-mediated Pyroptosis
复制标题
暴露于 X 射线通过 HMGB1 介导的细胞焦亡导致小鼠出现抑郁样行为
DOI：
10.1016/j.neuroscience.2021.11.023
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发表时间：
2021-11
期刊：
影响因子：
3.3
通讯作者：
Xuan Yi
中科院分区：
文献类型：
--
作者：
Lixing Xu;Haiqin Huang;Tianqing Liu;Tao Yang;Xuan Yi
电离辐射在工业和医疗领域的广泛应用导致了大脑对X射线的暴露增加。放射性脑损伤（radiation brain injury，RBI）可引起认知功能障碍和神经炎症，严重影响患者的健康。然而，X射线暴露和抑郁症状之间的联系及其详细的潜在机制尚未得到很好的研究。在此，我们研究了暴露于X射线的小鼠的潜在抑郁样行为，然后探讨HMGB1在这种损伤中的作用。我们发现，X射线刺激以剂量依赖的方式诱导前额叶皮层活性氧（ROS）的产生，导致小鼠抑郁样行为的发生。此外，X射线照射还可增加HMGB1的表达，激活NLRP3炎性信号通路和小胶质细胞，促进促炎细胞因子的释放，导致体内和体外的细胞凋亡和神经元丢失。此外，HMGB1抑制剂Gly可逆转X射线诱导的行为变化和神经元损伤。我们的研究结果表明，HMGB1介导的pyroptosis参与辐射诱导的抑郁症。
The widespread application of ionizing radiation in industrial and medical fields leads to the increased brain exposure to X-rays. Radiation brain injury (RBI) seriously affects health of patients by causing cognitive dysfunction and neuroinflammation. However, the link between X-ray exposure and depressive symptoms and their detailed underlying mechanisms have not been well studied. Herein, we investigated the potential depression-like behaviors in mice exposed to X-rays and then explored the role of HMGB1 in this injury. We found that X-ray stimulation induced the generation of reactive oxygen species (ROS) in the prefrontal cortex in a dose-dependent manner, leading to the occurrence of depression-like behaviors of the mice. Moreover, X-ray exposure increased the expression of HMGB1, activated NLRP3 inflammasome signaling pathway and microglial cells, and then facilitated the release of pro-inflammatory cytokines, resulting in the pyroptosis and neuron loss bothin vivoandin vitro. Additionally, glycyrrhizin (Gly), which is a HMGB1 inhibitor, reversed X-ray-induced behavioral changes and neuronal damage. Our findings indicated that HMGB1-mediated pyroptosis was involved in radiation-induced depression.
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