Exposure to X-rays Causes Depression-like Behaviors in Mice via HMGB1-mediated Pyroptosis. (15th January 2022)

• Record Type: Journal Article
• Authors: Xu, Lixing; Huang, Haiqin; Liu, Tianqing; Yang, Tao; Yi, Xuan
• Is Part Of: Neuroscience. Volume 481(2022)
• Page Start: 99
• Page End: 110
• Publication Date: 2022-01-15
• Subjects: AD Alzheimer's disease -- AIM2 absent in melanoma 2 -- ASC apoptosis-associated speck-like protein -- BBB blood–brain barrier -- CNS central nervous system -- CUMS chronic unpredictable mild stress -- DAMPs danger-associated molecular patterns -- FST forced swimming test -- Gly glycyrrhizin -- GSDMD gasdermin D -- HMGB1 high-mobility group box1 -- OPT open field test -- PAMPs pathogen-associated molecular patterns -- PFD pore-forming domain -- PRP pattern recognition receptors -- RBI Radiation brain injury -- RD repressor domain -- ROS reactive oxygen species -- SPT sucrose preference test -- TST tail suspension test; radiation brain injury -- depression-like behaviors -- HMGB1 -- NLRP3 -- pyroptosis; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2021.11.023
• Languages: English
• ISSNs: 0306-4522

Abstract

Graphical abstract: Highlights: X-rays caused the depression-like behaviors, microglial activation, and neuronal apoptosis in mice. ROS production and overexpression of HMGB1 from neurons participated in radiation-induced brain damage. NLRP3/ASC/Caspase-1-mediated microglial pyroptosis contributed to neuronal damage after X-ray challenge. Abstract: 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 both in vivo and in 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.