• Luodong Yang, Wenlong Xing, Yan Shi, Min Hu, Bin Li, Yuanyuan Hu, and Guiqing Zhang.
• First Affiliated Hospital of Shihezi University, Shihezi, China.
• Neuroscience. 2024 Sep 13; 555: 156166156-166.

AbstractInflammatory and myelin changes may contribute to the pathophysiology of post-traumatic stress disorder (PTSD). The NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3), a brain inflammasome, is activated in the hippocampus of mice with PTSD. In other psychiatric disorders, NLRP3 expression has been associated with axonal myelination and demyelination. However, the association between NLRP3 and myelin in rats with PTSD remains unclear. Therefore, this study aims to investigate the relationship between the NLRP3 inflammasome and myelin in the hippocampus of rats with PTSD. A rat model of post-traumatic stress disorder was established using the single-prolonged stress (SPS) approach. Hippocampal tissues were collected for the detection of NLRP3 inflammasome-associated proteins and myelin basic protein at 3, 7, and 14 days after SPS. To further explore the relationship between NLRP3 and myelin, the NLRP3-specific inhibitor MCC950 was administered intraperitoneally to rats starting 72 h before SPS, and then alterations in NLRP3 inflammasome-associated proteins and myelin were observed in the PTSD and control groups. We found that NLRP3 and downstream related proteins were activated in the hippocampus of rats 3 days after SPS, and the myelin content in the hippocampus increased after SPS stress. MCC950 reduced the expression of NLRP3-related pathway proteins, improved anxiety behaviour and spatial learning memory impairment, and inhibited the increase in myelin content in the hippocampal region of rats after SPS. In conclusion the study indicates that NLRP3 has a significant role in the hippocampal region of rats with PTSD. Inhibition of the NLRP3 inflammasome could be a potential target for treating PTSD.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

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